Sedation and analgesia are an integral part of the management of critical patients in the Intensive Care Unit (ICU). The aim of sedoanalgesia is to offer patients maximum comfort with safety, reducing anxiety and disorientation, facilitating sleep, and ensuring adequate pain control. This likewise contributes to avoid interferences with the medical and nursing care received.1 Critically ill patients in the ICU are at risk of suffering anxiety, agitation, aggressivity, delirium and withdrawal syndrome (opioids, alcohol, nicotine, etc.). An accurate diagnosis of these clinical manifestations is crucial, since adequate management is dependent upon it.2

The objectives of the present guide are to offer a series of recommendations on the use of sedation and the management of pain in adult patients admitted to the ICU, with or without tracheal intubation (nasal or orotracheal) (TI) and ventilatory support, and/or with certain conditions or diseases. The recommendations are based on a consensus of experts in Critical Care Medicine from different member countries of the Federación Panamericana e Ibérica de Sociedades de Medicina Crítica y Terapia Intensiva (FEPIMCTI). The guide is transparent as regards the literature supporting the level of evidence, the recommendations, and the methodology used in developing the guidelines, and can be adopted in any ICU.

In selecting the recommendations, the economic aspects (cost/effectiveness) addressed in global studies were not taken into account, since the concrete circumstances of each individual country can imply large variations in terms of applicability. The full technical report is available and can be requested from the guide coordinator via e-mail: edgarcelis.mdgmail.com.

The recommendations have been grouped into different sections, according to the specific conditions of the patients involved:

• A.

  Patients requiring conscious or cooperative sedation

• B.

  Monitorization of sedoanalgesia

• C.

  Patients with delirium and withdrawal syndrome

• D.

  Patients without endotracheal intubation or ventilatory support

• E.

  Patients with endotracheal intubation and mechanical ventilation

• F.

  Patients undergoing withdrawal of the endotracheal tube and mechanical ventilation

• G.

  Special populations: trauma patients, elderly subjects, pregnant patients and burn victims

• H.

  Sedoanalgesia in the immediate postoperative period of cardiovascular surgery

• I.

  Neurological and neurocritical patients

• J.

  Patients with kidney or liver failure

• K.

  Patients requiring special procedures (tracheostomy, thoracic catheters or tubes, peritoneal lavage, wound or burn lavage and debridement)

• L.

  Non-pharmacological strategies or complementary treatments

This guide does not cover the pediatric population or adults with conditions different from those cited above, such as transplant recipients, patients with brain death in the context of organ donation, or psychiatric patients.

The guide has been developed for use by physicians, nurses and physiotherapists (therapists) involved in the management of critically ill adult patients, though it can also prove useful in teaching activities involving residents and students.

This guide is presented as a list of recommendations referred to each question of the selected topic.

All critical patients have the right to receive adequate pain management where required

Grade of recommendation: strong. Level of evidence: low (1C).

Which are the most sensitive scales and elements for the monitorization and diagnosis of agitation?

A1. Objective evaluation is recommended of the presence and magnitude of agitation in all patients at risk of developing the condition in the ICU, based on a validated measurement scale (Richmond Agitation Sedation Scale [RASS] or Sedation-Agitation Scale [SAS]). This should be done systematically by trained personnel.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: Agitation is defined as frequent movements of the head, arms or legs, and/or disadaptation from the ventilator, persisting despite attempts by the supervising medical team to calm the patient.5,6 Agitation can occur due to toxicity of the central nervous system (CNS) secondary to drugs or other common critical patient conditions.7,8 Agitation exhibits a vicious circle resulting from a feedback mechanism in which the defensive reaction of the supervising medical team induces further agitation in the patient, with the risk of physical aggression and the tearing out of tubes, catheters and the endotracheal tube.9,10 The increase in oxygen demand in turn can lead to myocardial ischemia or other forms of organ failure in the seriously ill patient–thus justifying the need for quick and effective treatment.2,11,12

The Ramsay sedation scale (Table 3)13 was specifically validated more than 30 years ago for assessing the level of sedation. It contemplates only one agitation category, however, and so is of very limited use in quantifying the level of agitation.

In recent years more effective scales have been developed for evaluating agitation. Those offering the greatest validity and reliability include the Motor Activity Assessment Scale (MAAS),14 the SAS (Table 4)15,16 and the RASS (Table 5).17 The RASS and SAS scales are easy to use and remember, and this in turn favors their acceptance among the ICU personnel.17,18

Actigraphy, which measures movements recorded by an accelerometer affixed to a body extremity, shows good correlation to changes in neurological state as evaluated by sedation and pain scales, and could be useful for the early identification of agitation and its management.19

What are the factors that contribute to the development of agitation?

A2. It is advisable for the personnel attending the patient to assess and quantify the presence of agitation risk factors, with the aim of ensuring early treatment of such factors.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: The factors contributing to the development of agitation can be classified according to origin as follows5,6,20:

• 1.

  Exogenous (external) or toxic-organic origin. Agitation is produced by the action of toxic agents or in the course of medical diseases. These episodes are of sudden onset. In the case of drugs or substances of abuse, agitation results from overdose, adverse reactions or privation.

  The substances of abuse capable of causing agitation include alcohol (delirium tremens and hallucinations), smoking (privation),21 stimulants, marihuana and hallucinogens. The causal drug substances in turn include atropine, corticosteroids, phenytoin, barbiturates, phenothiazines, tricyclic antidepressants and disulfiram. The toxic-organic causes include epilepsy, subdural hematoma, cerebrovascular events, hypertensive encephalopathy, subarachnoid hemorrhage, intracranial tumors, sepsis, human immunodeficiency virus (HIV) infection with involvement of the CNS, hypothyroidism, puerperal psychosis, fever22 and hypoglycemia. Agitation also can manifest in encephalopathy associated to liver failure and renal failure.

• 2.

  Psychogenic origin. Agitation can result from situations of stress in patients with a susceptible personality and who easily suffer decompensation.

• 3.

  Endogenous origin. Agitation results from schizophrenic psychosis or maniac-depressive psychosis.

¿In which situations can conscious or cooperative sedation be considered indicated?

A3. Conscious or cooperative sedation is recommended in those patients who do not need deep sedation, and particularly in those who require periodic evaluation of consciousness due to some critical condition or complex procedure such as the introduction of noninvasive MV, the adaptation to spontaneous invasive MV modes, or during the endotracheal tube withdrawal process, especially in patients at risk of suffering serious neurological complications.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: Conscious or cooperative sedation can be defined as the minimum lowering of consciousness allowing the patient to maintain a permeable airway. From a more operative perspective (that of the patient bedside), it can be regarded as sedation in which the patient maintains an appropriate response to verbal or tactile stimulation, with maintenance of the airway reflexes, and with adequate spontaneous ventilation. The cardiovascular situation usually remains stable.23–25

Conscious or cooperative sedation has been used to shorten the duration of MV26–31 and the time from the start of weaning to extubation28; to shorten the stay in the ICU26,28,31,32 and in hospital30; to reduce the frequency of tracheostomy33; and to reduce the incidence of psychological disturbances during hospitalization or after discharge,32 including delirium29 and post-traumatic stress syndrome.27 In this context, a lesser incidence of delirium is associated to increased survival.29,30

Sedation can be provided during different therapeutic, diagnostic or surgical procedures; when frequent neurological evaluation is required; during the introduction of noninvasive MV; for adapting to spontaneous invasive MV modes; or during the TI removal process. Sedation is to be administered carefully, since it can be associated to adverse effects such as agitation, particularly in groups of patients subjected to MV and with disorders related to alcohol or drug abuse.34

Different methods for providing conscious sedation have been described, including the use of sedation protocols and algorithms, with or without daily interruption of the sedatives; patient wakening each day with or without spontaneous ventilation tests; the use of analgesia-sedation instead of hypnotic sedation; or the administration of new drugs with a lesser depressive effect upon the respiratory center.26–31,33 “Non-sedation” with the associated use of opioid analgesics could be regarded as a variant of conscious sedation.30

A4. The use of dexmedetomidine, fentanyl, remifentanil, propofol (boluses or infusion), or midazolam (only rescue boluses), in doses titered according to response, is recommended for conscious sedation in minor therapeutic, diagnostic or surgical situations in the ICU.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: Dexmedetomidine, a highly specific, short-acting α2-agonist, produces analgesia, anxiolysis and sedation that has been described as conscious sedation, reducing mental state disorders such as delirium.35,36 On the other hand, dexmedetomidine does not produce clinically significant respiratory depression–a fact that facilitates the management of these patients from the respiratory perspective and as regards the maintenance of airway permeability.37–43

Fentanyl, remifentanil and propofol can afford conscious sedation at variable doses and times, conditioned to the pharmacokinetic characteristics of each drug.44 Metabolite accumulation must be taken into account when using continuous infusions. On the other hand, it always must be remembered that midazolam and propofol do not produce analgesia.20,23–25,37,39–43,45–54

A5. The use of droperidol combined with opioids for neuroleptoanalgesia requires caution, with evaluation of the risk–benefit ratio for each patient, due to the appearance of extrapyramidal symptoms and the possible risk of torsades de pointes tachycardia.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: Droperidol, a fast- and short-acting butyrophenone, is useful for the treatment of psychomotor agitation and aggressivity. The doses are highly variable (from 0.625 to 1.25mg in bolus form, and from 5 to 25mg in infusion over 24h). Its adverse hemodynamic effects must be taken into account: vasodilatation, hypotension and tachycardia. It has no significant analgesic effect, and so is usually combined with an opiate.

However, its reported adverse effects include extrapyramidal symptoms and possible lengthening of the QT-interval, with the consequent risk of torsades de pointes tachycardia–though this effect has not been clearly demonstrated at low doses.55–57

Remifentanil has been used in anesthesia. Despite its brief effect and negligible accumulation, the use of this drug for the conscious sedation of critical patients requires very close monitorization and caution, since small dose increments can cause a loss of airway control.

What are the benefits of systematically evaluating sedoanalgesia in the critical patient?

B1. Protocolization of a systematic evaluation of pain and analgesia is recommended.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: Monitorization improves the effective management of pain, allowing better adjustment of the sedating and analgesic medication.58 Many studies have shown that adequate monitorization of sedoanalgesia allows us to reduce the time on MV, the duration of stay in the ICU, and the number of nosocomial infectious complications, particularly ventilator-associated pneumonia (VAP).59–65 Some authors have even reported a decrease in mortality following the introduction of systematic sedoanalgesia monitorization.66

What are the best tools for identifying pain in critical patients?

B2. The use of a validated scale is recommended, based on patient personal scoring of pain, whenever possible.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: Pain remains a frequent problem in critical patients, and can even be caused by routine techniques and care such as postural changes.67 A number of approaches can be used to identify pain68: we can try to have the patient report pain personally; assume that pain is felt when maneuvers potentially capable of causing pain are produced; we can use a validated behavior indicator scale; ask the patient relatives whether they believe that the patient suffers pain; and we can assess the response to analgesia.

Since pain is a subjective experience, the best evaluation of pain is that made by the patient in person.69 Different scales have been developed to quantify pain in critical patients. The most widely used instruments are based on a numerical or dimensional (length) scoring system (visual numerical scale, visual analog scale) displayed in a horizontal or vertical direction, in which the patient scores the intensity of the experienced pain.69–71 It is important to make the patient understand what kind of information we are seeking, and to use instruments of sufficient size, particularly in patients with sensory difficulties. A comparative study of these scales showed the maximum sensitivity and the greatest negative predictive value in discriminating pain to be obtained with the expanded-size visual numerical scale.71 On the other hand, most failures with these scales were observed in the more seriously ill patients or in individuals suffering delirium.

B3. The use of a validated scale is recommended, based on pain-related behavior indicators in patients who are unable to communicate.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: When the patient is unable to explain or express his or her pain, identification of the latter becomes complicated and requires the use of specific tools, generally based on physiological changes or behaviors associated to pain. The lack of an established gold standard has caused the development of many of these pain measuring instruments to be based on clinimetrics. Their application is therefore strongly conditioned to adequate validation (i.e., ensuring that they effectively measure what they are intended to measure) and reproducibility (i.e., affording the same results over time and with different observers).

The Behavioral Pain Score (BPS) (Table 6) uses a scale from 1 to 4 to score the facial expression of the patient, the posture of the upper extremities, and synchronization with MV. Higher scores imply increased intensity of pain.72 This scale has been validated by groups independent of the group that developed the instrument,73 and has demonstrated adequate correlation to the subjective scales.74 A modified version has even been developed for use in non-intubated patients, replacing the item adaptation to MV with the item vocalization.75

Other groups have developed different instruments for the identification of pain, based on behavior indicators. In this context, particular mention can be made of the Critical-Care Pain Observation Tool (CPOT)76,77; the Face, Legs, Activity, Cry, Consolability scale, developed from the pediatric COMFORT scale, and also applicable to children78; the Campbell scale69,79; or the recent modification of the latter scale designed for better adaptation to ventilated patients (the Scale of Behavior Indicators of Pain [ESCID]).80 Although the mentioned instruments have been developed with a process for the validation of adequate content, construction and criteria, the limited experience with their use to date means that there is not enough published evidence to recommend any concrete scale.

B4. It is recommended that physiological parameters isolatedly should not be used to identify pain, since they are nonspecific.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: Pain is associated with physiological changes. In this sense, we can observe an increase in heart rate, increased blood pressure, or dilation of the pupils, among other phenomena. When these changes occur suddenly and are intense, we can suspect that the patient is experiencing pain. However, these alterations often manifest irregularly, and the characteristics inherent to critical patients cause them to be nonspecific.81,82 In the development stage of the CPOT scale, the authors included a series of physiological indicators that were subsequently removed, since they were unable to improve the discriminating capacity of the behavioral components of the instrument.82

What are the best tools for controlling the level of sedation (and for evaluating the degree of agitation) in the critical patient?

B5. A validated scale measuring the depth of sedation based on patient capacity to respond to stimuli is recommended. The selected scale should quantify both the level of sedation and the degree of agitation.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: A number of clinical scales have been developed for documenting the depth of sedation according to the type and intensity of the physical stimulus needed to elicit a patient response. In this context, the Ramsay scale,13 developed over 35 years ago, remains the most widely used instrument. The Ramsay scale is very easy to use and is well accepted by the nursing personnel.83 It scores the patient condition according to 6 levels – only one of which corresponds to agitation. Among other instruments developed to evaluate sedation, mention can be made of the Vancouver Interaction and Calmness Scale,84 the Observer's Assessment of Alertness/Sedation Scale,85 the Adaptation to the Intensive Care Environment (ATICE),86 or the MAAS14–though currently the most widely used instruments are the SAS,15 the RASS18 or the ATICE.

The SAS scale comprises 7 categories, ranging from the absence of patient reactivity or responsiveness to dangerous agitation. It has been validated by several groups and is well accepted by the nursing personnel87,88 for documenting both the degree of sedation and the degree of agitation. The ATICE scale86 comprises 5 categories, of which two correspond to the consciousness domain and three to the tolerance domain. Its use within a sedation management algorithm in critical patients without brain injury has been associated to a shortening of the duration of MV and ICU stay.60 The RASS scale in turn starts from level zero in an alert and calm patient, and quantifies agitation in terms of four positive degrees and the depth of sedation in terms of 5 negative degrees. This instrument has been adequately validated and is well accepted,17 and moreover shows good correlation to the Ramsay scale.89 It is easy to use, and offers the advantage of constituting a component for the identification of delirium by means of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU)90 (Table 7). The RASS scale is regarded by the authors of the present recommendations as the instrument of choice.

What is the role of monitorization of the depth of sedation based on the bispectral index (BIS) in the critical patient?

B6. Use of the BIS is recommended only to avoid under- and over-sedation in patients requiring neuromuscular block, or in which utilization of the clinical scales is not possible.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: The use of techniques based on the electroencephalogram (EEG) for confirming unconsciousness in the operating room during surgery has led to the evaluation of these systems in the management of sedation in other settings, including the ICU. Among these systems, mention must be made of entropy and particularly of the bispectral index (BIS), which is the most widely used and evaluated of all the techniques.91,92 The BIS is an adimensional parameter derived from the EEG tracing and which ranges from 0 (absence of brain activity) to 100 (fully alert). A rating of between 40 and 60 is considered appropriate for surgical anesthesia.91

Different studies have examined the correlation between BIS and the clinical scales, with varied results, though some authors consider performance of the index to be acceptable.93–98 In general, the results have not been considered adequate for adjusting sedoanalgesia.99–101 The main cause of such poor correlation is the artifacts produced by the electromyogram,102–105 and which logically disappear when neuromuscular blockers are used. Profound depression of brain activity is reflected by the BIS, but not by the clinical scales.106

Due to the above considerations, the prevalent opinion is that the BIS should not be used when the clinical scales can be applied.107–110 In this context, the main advantage of BIS would be to allow the control of sedation in patients under neuromuscular block,111 where the recommendation of BIS 40–60 for surgical anesthesia would be appropriate. It is important to underscore that sedation below BIS 40 and an increase in suppression rate (percentage of isoelectric ECG recordings) have been associated to increased patient mortality.112

The BIS has also been used as a prognostic tool after cardiorespiratory arrest, as a marker of brain death, for the monitorization of neurocritical patients, and as an indicator of the degree of hepatic encephalopathy. Such indications fall beyond the scope of these recommendations, however, and in general little supporting evidence can be found in the literature.

B7. The use of BIS is recommended for the evaluation of consciousness in patients with fulminant liver failure and encephalopathy on the active waiting list for liver transplantation, for follow-up before and after organ grafting.

Grade of recommendation: strong. Level of evidence: weak (1C).

Justification: The use of BIS in anesthesia has been validated for assessing alertness or awakening. It has been recommended particularly in total intravenous anesthesia, since it is noninvasive and easy to interpret. In patients with fulminant liver failure, increases in BIS were seen to occur shortly before recovery was observed on the Glasgow coma scale in the postoperative period of liver transplantation.113

What are the recommendations for the management of patients with anxiety and agitation admitted to the ICU?

D1. The start of sedation in the agitated critical patient is recommended only after affording adequate analgesia and treatment of the potentially reversible causes.

Grade of recommendation: strong. Level of evidence: low (1C).

D2. The objective of sedation in each patient should be established and redefined periodically. Treatment response should be evaluated on a continuous basis and systematically documented.

Grade of recommendation: strong. Level of evidence: low (1C).

D3. In patients without TI and/or without ventilatory support, it is advisable to use drugs with a low risk of producing respiratory depression and severe hemodynamic adverse effects, such as haloperidol and dexmedetomidine.

Grade of recommendation: strong. Level of evidence: low (1C).

Is drug treatment useful in uncooperative patients subjected to noninvasive MV?

D4. Sedation with drugs that do not cause respiratory depression in uncooperative patients subjected to noninvasive MV is recommended.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: Drug treatment in the agitated critically ill patient without an artificial airway may lead to lesser cooperation on the part of the patient. Moreover, drugs in themselves can cause agitation or airway loss, giving rise to acute emergency situations. Consequently, monitorization of the level of sedation is more important than the chosen sedation technique.192

In patients without TI we use the same drugs as in intubated patients. Administration in bolus form is advisable at the start, followed by infusion which should be adjusted according to the response obtained. Very agitated patients can be immobilized while the appropriate drugs are administered via the intravenous route.192

The most important element in sedation of the agitated critical patient without MV is the physical presence of personnel adequately trained in airway management.192 The appropriate choice of sedating medication is often difficult, and depends on the individual needs. If quick awakening is required, as in neurological patients, propofol is the recommended drug. Haloperidol has been the preferred drug in delirium. Benzodiazepines are not advised, since they worsen agitation. The drug dosage required for adequate sedation also varies in the critical patient depending on the comorbidity, interaction of the sedative with other drugs, and the response to treatment193 (Fig. 2).

Figure 2.

Algorithm for sedation and analgesia in patients without tracheal intubation.

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In recent years there has been an increase in the use of noninvasive MV in the ICU. This ventilation mode is mainly indicated in cases of acute respiratory failure (ARF), with the purpose of improving arterial oxygenation, increasing alveolar ventilation, reducing respiratory effort and avoiding TI. Noninvasive MV reduces mortality and the need for intubation in patients with COPD and respiratory failure when employed both in the ICU and in hospitalization. In the ICU, noninvasive MV also reduces the duration of stay.194 Patient tolerance is important to ensure the efficacy of noninvasive MV. However, this assisted ventilation mode often reduces patient comfort, causing anxiety and difficulty in synchronizing the patient with the ventilator.

The chosen treatment schemes vary, though drugs that cause respiratory depression should be avoided.195 Of the existing substances used for sedation, the only drug that does not produce respiratory depression is dexmedetomidine.195,196 Midazolam195 or remifentanil197,198 at low doses and under close medical monitorization can also be used.

In a clinical trial of 41 patients subjected to noninvasive MV, both dexmedetomidine and midazolam were found to be effective in reaching the desired RASS score, and maintained the same respiratory frequency and gas exchange parameters. In the dexmedetomidine group, two patients required dose adjustment, versus three in the midazolam group.195 Huang et al. also compared the effect of dexmedetomidine versus midazolam in 62 patients with cardiogenic lung edema that rejected noninvasive MV. The group treated with dexmedetomidine required less TI (21% versus 45%) (RR 0.47; 95%CI: 0.22–1.02) (p=0.06) and a shorter stay in the ICU (4.9 versus 8.5days) (p=0.04); mortality in the ICU was similar with both drugs (6% versus 10%).199

Should patient immobilization be carried out? When?

D5. The use of restraining measures is only recommended in clinically appropriate situations, not as a routine practice. When immobilization is used, its benefit must be clear and based on a Department protocol.

Grade of recommendation: strong. Level of evidence: low (1C).

D6. The immobilization measures should be as noninvasive as possible and capable of optimizing patient safety, comfort and dignity.

Grade of recommendation: strong. Level of evidence: low (1C).

D7. The rational use of immobilization and its duration should be documented in the clinical history. Written instructions are required.

Grade of recommendation: strong. Level of evidence: low (1C).

D8. Periodic evaluation of the possibility of suppressing the immobilization measures is recommended.

Grade of recommendation: weak. Level of evidence: low (2C).

D9. The use of analgesics, sedatives and neuroleptics is recommended for the treatment of pain, anxiety or psychiatric disorders in patients in the ICU, since they can lessen the need for immobilization. However, such drugs should not be administered in excess as a form of “chemical immobilization”.

Grade of recommendation: strong. Level of evidence: low (1C).

D10. The development of complications due to immobilization should be evaluated at least once every 4h.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: Immobilization is commonly used in the ICU to protect the patient from the risks associated to the accidental tearing out or removal of devices such as endotracheal tubes, nasogastric tubes, venous catheters, arterial catheters, drains and urinary catheters. It is also used to protect the healthcare personnel from unintentional injury due to alterations in the cognitive condition of the patient.200,201 Restraint may also be needed to limit patient movements when the latter are contraindicated, for example in spinal fractures, for facilitating procedures in which the patient cannot collaborate, and for facilitating the management of certain psychiatric patients.202 The most commonly used method is the limitation of mobility of the upper extremities through binding at wrist level (87%).201

Immobilization only should be used when alternative measures prove ineffective or cannot be used without placing the patient at risk. The non-pharmacological alternative measures include the limitation of noise, the avoidance of unnecessary patient awakening, and family cooperation. Immobilization may be required if such measures fail.

On prescribing immobilization, due consideration is required of the potential conflict between the perceptions of the medical-nursing team and the best interest of the patient. On one hand, we should evaluate the need to protect the patient from his or her involuntary actions, though we also must take into account that immobilization can worsen the symptoms of delirium and can cause injuries. On the other hand, the healthcare team caring for the patient must be protected from unintentional aggression by the agitated patient.

Immobilization should be used as briefly as possible, and its indication must be reflected in the clinical history. According to the norms of the Joint Commission on Accreditation of Healthcare Organizations,203 once the alternatives to immobilization have failed and instructions are given to immobilize the patient, the decision must be stated and duly explained in the clinical history. In actual practice, the suggestion to immobilize the patient usually originates from the nursing personnel. Each institution should develop its own program to ensure the quality of care, in accordance with the principles and policies for the adequate use of physical immobilization201 (Fig. 3).

Figure 3.

Fixation needs related to the type of patients and the use of devices for monitoring and/or treatment.

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The policies referred to mechanical immobilization in the ICU vary greatly throughout the world, even in the presence of similar technologies or nursing-patient relationships,204 and the prevalence of such measures also varies greatly (from 0% to 100%).205 Some studies have found a certain relationship between non-scheduled tracheal extubation and mechanical restraint.206,207 Mechanical immobilization has also been associated to an increased risk of suffering delirium115 and post-traumatic stress syndrome in patients discharged from the UCI,208 though the methodological designs of the studies do not allow the drawing of firm conclusions.

Are there physiological benefits of using sedation and analgesia during MV?

E1. The routine use of sedoanalgesia is recommended in patients subjected to mechanical ventilation with TI.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: A lack of adaptation to the ventilator produces many complications that can further worsen the condition of the critical patient, including respiratory acidosis secondary to hypoventilation and increased CO2production; hypocapnia due to hyperventilation; hypoxemia as a result of dyssynchrony between the patient and the ventilator; increased intrathoracic pressure with a decrease in venous return, cardiac minute volume and arterial pressure; and increased O2 consumption due to the rise in muscle activity.3,59,209–211

Sedation and analgesia are commonly indicated in critically ill patients who at the same time require other priority medications or treatments. The indication of sedation and analgesia is established empirically, with a choice of drug and dosage that often proves inadequate.212

Not all ventilated patients require some or all of these medications, as in the case of the patients with neuromuscular problems (e.g., Guillain–Barré syndrome), who require mild daytime sedation and nocturnal sedation in order to sleep. A patient with severe ARDS will probably need maximum levels of analgesia, sedation and, sometimes, muscle relaxation.213,214

Analgesia implies the absence of sensitivity to pain or to aggressive stimuli such as the presence of an endotracheal tube or the aspiration of secretions. It is very common in MV to use sedatives that “sleep” the patient, but which do not protect him or her from pain or the systemic reactions caused by it–including tachycardia, increased myocardial oxygen consumption, etc. If the administration of analgesics results in disappearance of the physiological alterations, then pain can be confirmed as having been the cause of such alterations.3,61,64

Sedation in the critical patient is indicated as basic treatment for anxiety and agitation. These two sensations, combined with MV, imply that sedation in these patients is unavoidable, at least in the early stages.3,211 There are differences in the way sedating agents are used in acute or short-lasting situations versus the prolonged sedation that accompanies MV. Such differences refer not only to the drug used, but also to the method of administration involved.

What are the recommendations for the management of sedation and analgesia in patients subjected to MV?

E2. The use of a scale for the evaluation of pain and depth of sedation is recommended in patients subjected to MV.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: It is important to carry out a reproducible evaluation of whether the analgesia we seek has been satisfactorily obtained. Since pain is essentially subjective, we should try to know the opinion of the patient, if possible. Since these are ventilated patients, subjected to TI, we can use a graphic pain scale (visual analog scale) that proves easy to understand, for example a line extending from “no pain” at one end to “maximum pain” at the other. In the case of sedated patients, in whom it is particularly common to underuse analgesia, it is important to evaluate the somatic and physiological equivalents of pain. Among the former, patient facial expression, movements and body posture can be clear indicators of pain, as in the BPS scale.215,216 In turn, among the physiological signs, the presence of tachycardia, hypertension, tachypnea and ventilator disadaptation, included in the Non-Verbal Pain Scale,215,216 requires us to consider the administration of analgesics, if not already administered, or to increase their dose.3,61,64

Another problem is the difficulty of assessing the depth of sedation. The use of scales for evaluating the depth of sedation during MV is recommended by most consensus guides on the subject. Sedation scales are a fundamental part of the protocols referred to the adaptation of patients with MV60,61,64,106 (Table 3).

E3. Implementation of the sedation and analgesia protocols preferably should be carried out by the nursing personnel. It is not advisable to apply this recommendation when there are not enough nurses available.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: With some exceptions, different authors have reported better results with the application of strict sedation and analgesia protocols controlled and applied by the nursing personnel of the ICU. However, it is clear that when the number of available nurses is insufficient, they cannot be overburdened by this additional task.34,65,217–230

E4. The routine use of deep sedation (RASS 1 to −3) in patients subjected to MV is not recommended.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: The levels of sedation differ from one type of patient to another. The adequate levels of sedation for ventilated patients are between 2 and 4 on the Ramsay scale or between 1 and −3 according to the RASS13,27,29,32,231–234 (Tables 3 and 5). In patients with MV due to complex situations (e.g., exacerbated COPD, severe asthma, ARDS), levels corresponding to Ramsay 3 or 4 or RASS −4 are recommended. With these levels of sedation we often observe anterograde amnesia–a situation which some authors associate to an increased incidence of delirium and post-traumatic stress.

It should be remembered that deep sedation corresponding to level 5 or 6 according to the Ramsay scale or RASS −5 may be useful only in sedation forming part of the treatment of intracranial hypertension, or in situations such as tetanus or malignant hyperthermia.235,236

E5. Whenever possible, it is advisable to use conscious or cooperative sedation with titrated doses of a continuous infusion of propofol or dexmedetomidine.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: A number of studies have shown this approach to shorten the duration of MV, the days of stay in the ICU, and the incidence and duration of delirium. Likewise, it has been reported that this strategy does not increase the incidence of myocardial ischemia.29,32,231–234,237,238

E6. Opioids are recommended as the analgesics of choice in the ventilated patient–the first line drugs being fentanyl and morphine–especially in patients requiring prolonged ventilation.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: The most important side effects of the opioids, which are regarded as the drugs of choice for analgesia in the critical patient, are respiratory depression, arterial hypotension, gastric retention and ileus. Despite these adverse effects, correct analgesia is a primary objective in the critical patient subjected to MV.3,59,61,64,210,239

Morphine, in sulfate or hydrochloride form, is the analgesic drug of choice for ventilated patients. Its advantages include analgesic potency, low cost, and an euphorizing effect. Morphine is to be administered via the intravenous route, starting with a loading dose followed by continuous venous infusion. The recommended loading dose is 0.05mg/kg administered in 5–15min. Most adults require continuous infusion of between 2 and 3mg/h, with levels of up to 4–6mg/h in some patients. During the continuous infusion of morphine it is common to need one or more bolus doses at the same dosage as the initial loading dose, in order to secure an adequate analgesic effect. If administration in bolus form is decided, it should be scheduled as repeated doses, once every 3h, attempting to adjust the dosage according to the therapeutic response obtained.3

Fentanyl is the analgesic drug of choice for ventilated patients with hemodynamic instability, or in patients with symptoms of histaminic release or allergy with the use of morphine. Fentanyl does not cause histamine release–a fact which may explain its lesser effect upon arterial pressure and bronchial smooth muscle. It has a relatively short half-life (30–60min), due to its rapid distribution. However, the prolonged administration of fentanyl gives rise to accumulation of the drug in the peripheral compartments, and extends its half-life (contextual half-life) to 16h. The drug is to be administered in continuous infusion at a rate of 1–2μg/kg/h, following one or more loading doses of 1–2μg/kg. The routine use of fentanyl is not recommendable in all patients, since its analgesic effect is similar to that of morphine; the drug tends to accumulate as a result of prolongation of its half-life; and its cost is usually greater.3

E7. It is advisable not to use meperidine, nalbuphine or buprenorphine in the critical patient.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: Meperidine has an active metabolite, normeperidine, which can accumulate and produce excitation of the central nervous system and seizures, particularly in patients with acute neurological damage.3

Nalbuphine and buprenorphine are usually prescribed to calm mild or moderate pain in the immediate postoperative period. It must be remembered that they can revert the effect of other opioids through interaction at receptor level. They can be used as an option when the traditional opioids are contraindicated.3

E8. Whenever possible, it is advisable to minimize or suppress the use of sedatives in prolonged MV, using the sedation scheme based on analgesia.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: A number of studies have reported a decrease in the number of days with MV and in the duration of ICU stay when the use of sedatives is suppressed or minimized by the administration of opioid analgesics in continuous infusion in patients with MV. The drug most widely used in the studies that propose this approach is remifentanil–its main advantage being rapid disappearance of the effect and independence of renal and/or liver function.31,36,240–243

Remifentanil is a synthetic opioid that exhibits practically no accumulation, since it is quickly metabolized by plasma esterases. It likewise does not accumulate in patients with kidney or liver failure. These properties imply that recovery from the effects of the drug takes place in only a few minutes, even after prolonged administration. The usual analgesic doses are 0.05–0.3μg/kg/min. Depending on the dose, remifentanil produces central depressor effects like other opioids. Some studies recommend its use in analgesia based sedation Schemes.36,240,241,242,243 The drug has also been used in the ventilator weaning process.244–246

E9. Midazolam, propofol or lorazepam are recommended as sedatives of choice in patients with MV requiring deep sedation corresponding to RASS −4 to −5 or Ramsay 4–6.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: There are differences in the use of sedating agents in acute or short-lasting situations and in deep sedation accompanying MV in patients with diseases such as those mentioned above (Fig. 4). These differences refer not only to the drug employed but also to the method of administration.247–251

Figure 4.

Algorithm for sedation and analgesia in patients with tracheal intubation.

(0.34MB).

All parenteral benzodiazepines cause anterograde amnesia, and it should be remembered that they do not have analgesic effects. Although the prototype drug for intravenous sedation is diazepam, it is no longer recommended, because: (a) it often causes pain and thrombophlebitis when administered through a peripheral vein; (b) administration in bolus form can lead to excessive sedation; (c) administration as a continuous intravenous infusion increases its half-life, reaching 7 days in some patients; and (d) the drug requires dilution in a large volume–which implies a risk of water overload in the context of prolonged administration. However, it is used in some centers because of its low cost and rapid mechanism of action when performing brief maneuvers (electrical cardioversion, TI), being indicated as a single bolus dose.3 Midazolam and propofol are the drugs of choice for brief sedation, as for example when maneuvering in TI at the start of MV. The usual midazolam dose for effective sedation during TI maneuvering or other brief procedures is 0.2mg/kg, which can be repeated in bolus doses of 0.07mg/kg until the desired sedation level is reached.3

Propofol is an intravenous anesthetic which at sub-anesthetic doses produces sedation and hypnotic effects, as well as a degree of anterograde amnesia. Propofol and midazolam have been shown to have the same sedative effect in comparative studies.3,252

Propofol offers fast action after the administration of an intravenous bolus (1–2min), due to its rapid penetration of the central nervous system, and its effect is short lasting (10–15min). When used in prolonged treatments, it should only be administered in continuous infusion with the precaution of using a central vein rather than a peripheral venous access. Propofol also significantly prolongs its half-life when administered for prolonged periods of time, due to accumulation of the drug in the lipid deposits–its half-life reaching 300–700min.252,253 In order to secure rapid sedation, as in TI maneuvering, bolus dosing at 2–2.5mg/kg is recommended. If we wish to keep the patient sedated, in the case of continuing with MV, a continuous infusion should be used at a starting dose of 0.5mg/kg/h, followed by stepwise increments of 0.5mg/kg every 5–10min, according to the clinical response obtained. A common maintenance dose is between 0.5 and 3mg/kg/h. The administration of propofol in bolus form usually produces a drop in arterial pressure that can reach 30% of the basal blood pressure value.254,255

In recent years, many studies have shown benzodiazepines (midazolam and lorazepam) to be associated with an increased incidence of coma and delirium in intubated and ventilated patients. This in turn results in longer periods of MV, a longer stay, and greater morbidity–mortality.29,32,35,36,231,233,234,256

Lorazepam is one of the drugs suited for prolonged sedation in the ventilated patient. This intermediate-acting benzodiazepine is less lipophilic than other drugs of the same group, and therefore undergoes less peripheral accumulation. In comparison with midazolam, lorazepam has a longer half-life and a similar capacity to produce anterograde amnesia. In view of its half-life, lorazepam is suitable for administration in intermittent bolus doses, though it can also be used in continuous infusion. Since the pharmacological latency period of lorazepam is longer than that of other benzodiazepines, it is advisable to start with a dose of diazepam or midazolam to induce rapid sedation. The lorazepam dose recommended as starting bolus or as “reinforcement” dose is 0.05mg/kg, to be repeated every 2–4h as required. In prolonged sedation, some authors advise the administration of a continuous infusion of lorazepam at doses of 0.025–0.05mg/kg/h. These doses are usually insufficient, however, and can be doubled or tripled in some patients. A number of authors have reported elevated propyleneglycol levels that could prove toxic under these circumstances, though no evident clinical effects have been described.251 The intravenous form of lorazepam is not available in all countries.3

E10. The use of a sedative with a shorter half-life, such as dexmedetomidine, is recommended for reducing the duration of MV and the incidence of delirium in patients that can tolerate mild sedation levels (RASS 1 to −3 or Ramsay 2–3).

Grade of recommendation: strong. Level of evidence: moderate (1B).

E11. Dexmedetomidine is recommended as a useful drug for postoperative sedation and analgesia in patients requiring MV for short periods of time, and particularly in septic patients.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: Dexmedetomidine is an α2 agonist with greater affinity for α2 receptors than for α1 receptors. The drug inhibits the postsynaptic receptors, thereby inducing not only a drop in blood pressure and heart rate but also a clear anxiolytic and sedating effect. Its action at spinal receptor level also affords an analgesic effect. The initial loading dose in ventilated patients is 1μg/kg in 10min. The maintenance infusion rate is 0.2–1.4μg/kg/h, considering that the side effects are greater with doses above 0.7μg/kg/h. The maintenance dose often must be increased when using dexmedetomidine in prolonged treatments. The loading bolus can cause bradycardia accompanied by hypotension, which in some cases can be sustained over time, particularly in hypovolemic and elderly patients. Some authors recommend obviating the loading doses in order to avoid these side effects.

This drug does not produce respiratory depression or gas exchange alterations, and can be safely administered in patients with renal failure. Dexmedetomidine likewise does not cause alterations in adrenal cortical or inflammatory function. In view of these properties, some authors choose dexmedetomidine as the best sedative for weaning from MV, and for conscious sedation. Observational studies also show that dexmedetomidine appears to reduce the incidence of delirium and the mortality rate among septic patients (hazard ratio 0.3; 95%CI: 0.1–0.9).29,32,248,253,256–260 These findings must be confirmed by further studies, however. The dosage should be lowered in patients with liver failure.13,35,36,38,42,248,259,261–264

E12. It is advisable not to use etomidate in sedoanalgesia for patients subjected to MV.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: Etomidate should be contraindicated in the critical patient, due to its capacity to produce adrenal gland insufficiency.265,266

E13. Daily interruption of the infusion of sedatives and analgesics is recommended in order to reduce the total administered dosage.

Grade of recommendation: strong. Level of evidence: moderate (1B).

E14. The daily interruption of sedoanalgesia is recommended, with performance of a spontaneous ventilation test (when allowed by the respiratory condition of the patient), with the purpose of reducing the development of complications and the duration of MV.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: Kress et al.,267 in a clinical trial involving 128 patients treated with the same sedoanalgesic scheme (midazolam or propofol plus morphine) for maintaining a Ramsay score of 3 or 4, compared the effect of the daily interruption of sedoanalgesia from 48h after the start of treatment (experimental group) versus the interruption of sedoanalgesia according to physician criterion (control group). The mean duration of MV in the experimental group was 4.9days versus 7.3days in the control group of (p=0.004); the duration of stay in the ICU was 6.4 and 9.9days (p=0.02), respectively. The incidence of complications (e.g., accidental withdrawal of the endotracheal tube) was 4% and 7%, respectively. A decrease in the total dose of sedatives and morphine was observed among the patients treated with midazolam (40% lesser dosage in the experimental group), but not in those treated with propofol.

Similar results have been recorded in a retrospective study that likewise registered a lesser incidence of pneumonias, sinusitis, bacteremia and deep venous thrombosis in patients subjected to the daily interruption of sedoanalgesia.267,268 The daily suspension of sedoanalgesia should not be carried out on a routine basis in patients with intracranial hypertension, MV involving non-conventional ventilatory modes or with hemodynamic instability. Individual assessment is required in such cases.267,268

There have been reports of improved sleep performance with this practice.269 Some authors have not been able to reproduce these data, however.34 If the patient is disadapted to the ventilator, already has adequate analgesia and a Ramsay score of 4 or a RASS score of under −3, use can be made of neuromuscular relaxants. It is not advisable to progress to higher sedation levels to achieve adaptation to the ventilator. In patients receiving an infusion of muscle relaxants, we must wait for their effects to subside before deciding the daily suspension of sedoanalgesia. If the patient does not present disadaptation to the ventilator after the period of time considered sufficient for elimination of the paralyzing effect, we should proceed to suspend midazolam as recommended for the global patient population.34,253,267–273

E15. The monitorization of sedation with BIS is recommended in patients subjected to MV with acute neurocritical disease or under the effects of neuromuscular relaxants, in order to avoid infra- or oversedation.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: Olson et al.,101 in a clinical trial of 67 neurocritical patients subjected to MV and continuous sedation with propofol, evaluated the effect of two nursing-controlled protocols: Ramsay 4 versus Ramsay 4 plus BIS 60–70 during 12h. Addition of the BIS to the Ramsay scale was associated with a decrease in the dose of propofol (14.6 versus 27.9μg/kg/min) (p=0.003).

E16. It is advisable to consider a decrease in sedatives and analgesics in patients subjected to MV after performing tracheostomy.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: When MV is prolonged, the patient should not continue with the endotracheal tube.

It is not the purpose of this document to discuss the timing of tracheostomy or the best way of performing the technique. The absence of a tube through the glottis considerably lessens patient pain. Likewise, the level of sedation can be lowered under these circumstances, because the patient is more stable from the hemodynamic, neurological and respiratory perspectives. Nieszkowska et al., in a retrospective observational study of 72 patients subjected to MV, found the need for sedative and analgesics to decrease after tracheostomy.274

E17. It is suggested not to routinely increase the dose of sedatives, when accompanied by an infusion of morphine, in patients subjected to permissive hypercapnia.

Grade of recommendation: weak. Level of evidence: low (2C).

Justification: Permissive hypercapnia is a MV technique that can be used in two types of situations. The first corresponds to patients with severe airflow obstruction (asthma, COPD) requiring a low respiratory frequency and low tidal volumes in order to avoid high pressures in the airways and air trapping. The second refers to patients with severe ARDS who develop hypercapnia on being ventilated with a protective strategy.275 These situations often require the use of muscle relaxants.276 Vinayak et al.,277 in a retrospective study of 124 patients subjected to MV, found that in the first three days the patients with permissive hypercapnia treated with midazolam (n=13) did not require more doses than those who did not have permissive hypercapnia (n=51). In contrast, the patients with permissive hypercapnia treated with propofol (n=10) required greater doses than those who did not have hypercapnia (n=50). Other studies have obtained similar results.278,279

E18. In patients with ARDS, PaO2/FiO2<150, subjected to protective MV, consideration of the use of non-depolarizing neuromuscular blockers in continuous infusion is suggested during the first 48h.

Grade of recommendation: weak. Level of evidence: moderate (2B).

Justification: Needham et al. recently reported that patients with severe ARDS treated with a continuous infusion of non-depolarizing muscle relaxants (cisatracurium) during the first 48h of MV presented lesser mortality after 90 days, and a decrease in morbidity, with a shorter duration of MV, a briefer stay in the ICU, and a lesser incidence of organ failure and muscle weakness.276

What are the recommendations for patients with special conditions, such as individuals with COPD, ARDS, asthma, hemodynamic instability or multiorgan failure?

E19. Fentanyl is recommended as the analgesic of choice in patients with hemodynamic instability, bronchial asthma or COPD.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: Fentanyl does not give rise to histamine release–a fact that can explain its lesser effect upon arterial pressure and bronchial smooth muscle.3

E20. An early physical and occupational therapy protocol is recommended in intubated patients subjected to MV, with the aim of reducing the duration of MV.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: In a series of 109 patients, Schweickert et al. evaluated the efficacy of physical and occupational therapy in the first three days of MV during the daily waking periods using the prescribed standard treatment that included daily awakening but without physiotherapy until prescription of the latter by the primary care team. Early therapy was associated with a greater percentage of functional independence at discharge (59% versus 35%) (OR 2.7; 95%CI: 1.2–6.1) (p=0.02) and a lesser duration of delirium (2 versus 4 days) (0.02).188 Needham et al., in a prospective observational study lasting 6 months in 57 patients subjected to MV for four days or more and enrolled in an early physical rehabilitation protocol with the reduction of deep sedation, reported a decrease in the incidence of delirium, with improved functional mobility, and a shortening of stay both in the ICU and in hospital.233

E21. Music therapy is recommended as a non-pharmacological adjuvant to sedation in patients subjected to MV, particularly during weaning.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: Different studies have found music therapy to reduce anxiety, its physiological equivalents, and the administration of sedation during MV, particularly during weaning periods.280–282

What should be the pharmacological approach to patients undergoing withdrawal of MV and the oro/nasotracheal tube?

F1. A defined sedation and analgesia monitoring and dose adjustment protocol is recommended when withdrawal of the ventilator is planned, following resolution of the cause leading to the need for MV. This protocol should include daily evaluation of sedation, an awakening test and a spontaneous breathing test.30

Grade of recommendation: strong. Level of evidence: high (1A).

Justification: Patients undergoing withdrawal of MV and the tracheal tube must be in the waking state. All sedoanalgesia protocols must aim to prevent the accumulation of sedatives and analgesics, and the prolongation of their effect.

At this point the leading priority is to apply non-pharmacological measures for alleviating anxiety: the patient should receive a clear explanation of the situation, of the collaboration expected from him or her, and of the steps to be taken. Likewise, noise should be reduced to a minimum, along with the intensity of illumination, and flexible visiting hours should be allowed, since these are measures that help the patient in this phase. One of the basic principles for extubation is to assess sedation and determine whether its level is able to interfere with spontaneous breathing. Girard et al.30 in a study of 336 sedated patients subjected to MV, evaluated the combination of interrupting sedation and performing the spontaneous breathing test in the intervention group, versus use of the spontaneous breathing test in the control group. The patients assigned to the intervention group showed a clear reduction in the days without ventilation and in the duration of ICU stay (9.1 versus 12.9 days) (p=0.01). The mortality rate after 28 days showed no significant differences between the two groups (28% versus 35%) (p=0.21), though the difference in mortality after one year did reach statistical significance (44% versus 58%) (p<0.01). The interruption of sedation and the spontaneous breathing test can be regarded as standards of care.

F2. A defined sedation and analgesia monitoring and dose adjustment protocol is recommended, with daily suspension, when withdrawal of the ventilator is contemplated, once the cause leading to the need for MV has been resolved.

Grade of recommendation: strong. Level of evidence: high (1A).

Justification: During the withdrawal of MV and TI, the patient must be lucid and alert. If necessary, medication to control pain and psychomotor agitation should be provided.28,283,284

Which drugs may be contraindicated?

F3. It is advisable not to use midazolam or lorazepam in the withdrawal of MV.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: Prolonged sedation with midazolam or lorazepam is associated to a prolongation of the time on MV, the time of withdrawal of MV and the orotracheal tube, and of patient stay in the ICU, since drug accumulation can occur, with the prolongation of sedation.253,285–288

Are there drugs that might be indicated?

F4. Low-dose remifentanil in continuous infusion is recommended for the sedation and analgesia of patients subjected to weaning from MV.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: The choice of drugs depends on factors related to the patient (comorbidities, cause or indication of MV, time of MV), the pharmacological characteristics of the drugs, their adverse effects and costs.289 Pain can be one of the causes of withdrawal failure. In order to guarantee constant analgesia, continuous infusion is preferable to bolus dosing, since it allows more effective titration, a lesser total drug dose, and a shorter duration of MV. Bolus doses can be used via the intravenous route as rescue medication.253,285,286

Rozendaal et al. compared the effect of two analgesia and sedation protocols in 205 patients subjected to MV in the context of an open-label, cross-over clinical trial. One group received remifentanil, and propofol was only administered if sedation was not achieved at maximum doses (12μg/kg/h). The conventional group in turn received analgesia with morphine or fentanyl, and sedation with propofol, midazolam or lorazepam. The mean weaning time was 6h in the group treated with remifentanil and 25h in the group subjected to conventional treatment (p=0.0001), while the stay in the ICU was 6 versus 8 days (p>0.05), respectively.240 In the opinion of some authors, these results support the recommendation to use remifentanil in the weaning process.290

F5. Methadone via the enteral route is recommended in patients receiving opioids for more than 5 days and who are subjected to MV.

Grade of recommendation: weak. Level of evidence: moderate (2B).

Justification: In a group of 28 patients subjected to MV, 32% (95%CI: 13–51%) developed withdrawal syndrome after receiving opioids for 7 days or more.291 A recent double-blind, randomized controlled clinical study involving 68 patients showed that among the 54 survivors, the use of enteral methadone in subjects who had received opioids during more than 5 days reduced the weaning time from 7 days (95%CI: 2.5–11.5) to 4 days (95%CI: 1.99–6.01).292

F6. Dexmedetomidine is recommended in postsurgical patients.

Grade of recommendation: strong. Level of evidence: low (1C).

F7. Dexmedetomidine is recommended in patients with MV weaning difficulties and in patients with withdrawal syndrome.

Grade of recommendation: strong. Level of evidence: low (1C).

F8. Dexmedetomidine is recommended in patients with failed previous attempts of weaning from MV secondary to agitation and delirium.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: Dexmedetomidine is an effective and safe sedative for most postsurgical patients in the ICU. The advantages of dexmedetomidine are its α agonist effect, conscious sedation, a lessened need for opioids, and respiratory stability. However, the drug is associated with hypotension and bradycardia, which generally resolve spontaneously or with only minimum intervention in the form of volume replacement and sometimes atropine and low-dose vasoactive drugs.287,293–295

When the patient develops agitation, delirium, suffers anxiety or develops withdrawal syndrome, it is useful to maintain a minimum level of sedation using drugs with a short half-life.1

Delirium, agitation and withdrawal have been associated to adverse outcomes in patients subjected to MV, particularly during the withdrawal of MV. In this process, dexmedetomidine has been used to guarantee the success of weaning in patients with previous failed weaning attempts due to agitation. The benefits of dexmedetomidine are possibly more significant when used with daily interruption of sedation, a weaning protocol, and early mobilization.125,296–299

F9. Propofol is recommended in postsurgical patients.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: Propofol is the sedative of choice when quick patient awakening is required, due to the shorter waking time associated with this drug. The difference is more accentuated when the therapeutic objective is a Ramsay score of 4 or 5. In addition, the waking time is more predictable in patients administered propofol than in those receiving midazolam.253,285–287

What special considerations apply, and what are the pharmacological recommendations for the management of sedation and analgesia in these patients?

Trauma patients

G1. Propofol is recommended for the sedation of trauma patients requiring frequent neurological evaluations (Fig. 5).

Figure 5.

Algorithm for sedation and analgesia in trauma patients with and without neurological impairment.

(0.23MB).

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: The pharmacokinetic properties of propofol, resulting in fast recovery of patient consciousness within 10–15min after suspending infusion of the drug, have been commented in a number of publications.300–302 This characteristic is very useful in patients requiring frequent evaluations of central nervous system function.

G2. It is advisable to use propofol at doses of under 5mg/kg/h in order to avoid propofol infusion syndrome.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: Propofol infusion syndrome is defined as the presence of heart failure, metabolic acidosis and rhabdomyolysis.303 In this study the symptoms were evidenced 24–48h after the start of infusion. The mortality rate associated to this syndrome in patients administered propofol for the control of intracranial hypertension was 10%. The probability of appearance of the phenomenon is 1.93 for every mg/kg of increase over the mean dose of 5mg/kg/h (equivalent to 83μg/kg/min). None of the patients administered less than this dose developed the syndrome.303 The recommendation underscores the avoidance of propofol doses above 5mg/kg/h until the safety of other doses has been assessed.

G3. Use is recommended of protocols for sedoanalgesia and the detection of delirium in critical trauma patients.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: A controlled, prospective study involving patients that cannot receive daily interruptions of the infusion of sedatives found that objective evaluation using protocols for analgesia, conscious sedation and the detection of delirium reduces the days of MV and hospital stay in critical trauma patients.62

G4. Use of the CAM-ICU is recommended in the detection of delirium in trauma patients.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: A retrospective study compared 59 trauma patients treated with a protocol for sedation (RASS), analgesia (visual analog scale) and the estimation of delirium (Confusion Assessment Method for the Intensive Care Unit, CAM-ICU) versus 61 patients treated without this protocol two years earlier. During the period in which the protocol was used, the duration of MV was reduced from a median of 3.2–1.2 days (p=0.03), and the median duration of stay in the ICU was 5.9 versus 4.1 days (p=0.21), respectively.304

Are there benefits in using sedation and analgesia in patients during the postoperative period of heart surgery?

H1. It is advisable for all patients in the immediate postoperative period of heart surgery to receive adequate analgesia and sedation, in order to lessen the appearance of possible complications.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: The absence of pain and anxiety is a fundamental right of the patient, and moreover reduces the incidence of complications.67,319 Postoperative sedoanalgesia reduces morbidity in heart surgery. Tachycardia and catecholamine release contribute to the development of arterial hypertension, myocardial ischemia and atheroma plaque rupture. At the time of admission to the ICU, the patients are under the residual effects of anesthetics, and in this context the anesthetic technique used in the operating room is an important factor for defining the required grade of sedoanalgesia.

During the immediate postoperative period there is an interval in which MV is needed, and sedoanalgesia is therefore required while thermal homeostasis and hemodynamic stability are restored. Optimum sedation in this period minimizes cardiovascular response to stimulation, reduces the time required for awakening, and allows withdrawal of the endotracheal tube without increasing the incidence of cardiovascular complications.320 At present, with the use of fast-track anesthetic systems, the administration of short acting drugs allows rapid postanesthetic recovery.321

H2. Postoperative conscious sedation adequately controlling stress response is recommended. A sedation measurement scale should be used to control this effect (RASS score −1 and −2).

Grade of recommendation: weak. Level of evidence: moderate (2B).

Justification: Traditionally it was assumed that patients in the postoperative period of heart surgery require deep sedation in order to reduce the endocrine response to stress and prevent myocardial ischemia.320 However, there are no statistically significant differences in the stress response indicators (e.g., catecholamine and cortisol levels) between superficial and deep sedation. In contrast, those patients subjected to deep sedation experience greater myocardial ischemia, higher levels of pain, and prolongation of the duration of ventilatory support compared with those receiving mild sedation.322

H3. The use of remifentanil or other opioids and PCA is recommended as a first measure in the management of cardiovascular postoperative analgesia.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: The use of remifentanil/propofol in comparison with fentanyl/midazolam in patients during the postoperative period of cardiovascular surgery while subjected to MV was shown to maintain better levels of analgesia, reducing the duration of MV (20.7 versus 24.2h [p<0.05]) and the duration of stay in the ICU (46.4 versus 64.7h [p<0.05]).323 Following the withdrawal of MV, analgesia with morphine or its analogs remains the treatment of choice for the management of pain, thanks to its potency, with variations in the method of administration (i.e., in bolus form, as a continuous infusion, or as patient-controlled analgesia [PCA]).

No significant differences have been found on comparing the use of PCA with analgesia provided by the nursing personnel, since health professionals tend to closely monitor the presence of pain in these patients and offer analgesia in a timely manner.324 Likewise, no differences in the level of sedoanalgesia obtained have been found on comparing the use of PCA with peridural analgesia.325,326

H4. Consideration of the use of subarachnoid and/or peridural analgesia for the management of postoperative pain is suggested.

Grade of recommendation: weak. Level of evidence: moderate (2B).

Justification: The combination of general anesthesia with regional anesthesia has resulted in reduction of the time to withdrawal of the endotracheal tube and better pain control in heart surgery patients. The administration of intrathecal sufentanil, clonidine or morphine reduces the need for postoperative analgesia and affords better pain control. The use of intrathecal morphine is safe in comparison with the conventional administration methods.327–332 However, the administration of intrathecal morphine does not shorten the time to withdrawal of TI in comparison with placebo.333 On the other hand, the addition of epidural or subdural opioids to those administered via the intravenous route during surgery can produce respiratory depression and delay withdrawal of the endotracheal tube.334

In fast-track heart surgery protocols, the administration of low-dose intrathecal morphine is associated with a 40% decrease in the use of intravenous morphine during the first 24h after withdrawal of the endotracheal tube.335

Peridural analgesia using low doses of 0.125% bupivacaine improves the myocardial oxygen supply/demand ratio, increases subendocardial blood flow, and reduces postoperative hypercoagulability. Consequently, its use in combination with inhalatory general anesthesia has been associated to a lessened stress response among patients subjected to coronary surgery.336

There have been no reports of hematomas secondary to neuroaxial block. Nevertheless, while low, the risk exists and must be taken into account (1:150,000 for block peridural and 1:220,000 for subdural block).337

Globally, therefore, the risks and benefits of regional anesthetic techniques should be evaluated in each individual patient, considering that there is no definitive evidence supporting its use in securing faster withdrawal of the endotracheal tube, when compared with the traditional administration of intravenous opioids and nonsteroidal antiinflammatory drugs (NSAIDs).

It has been suggested that other techniques such as parasternal block, infiltration of the surgical wound, the use of paravertebral blocks and continuous infusions of local anesthetics can be useful as analgesic treatment in patients subjected to heart surgery.338–341

H5. The use of NSAIDs is suggested for the management of postoperative pain.

Grade of recommendation: weak. Level of evidence: moderate (2B).

Justification: NSAIDs allow us to reduce the dose of opioids, maintain or improve analgesia, and reduce the undesirable side effects of opioid drugs.342,343

Diclofenac, indomethacin and ketoprofen have been shown to be effective in the management of postoperative pain.343 However, these drugs are contraindicated in patients with coronary disease, renal failure, gastrointestinal bleeding and bronchospasm.

H6. The use of dexmedetomidine, remifentanil or their combination, the combination of low-dose propofol and midazolam, or the combination of propofol and fentanyl are recommended for postoperative sedation and analgesia.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: The use of dexmedetomidine significantly reduces the incidence and duration of delirium in patients in the postoperative period of cardiovascular surgery requiring sedation, when compared with midazolam and propofol, and when compared with patients treated with morphine only. At the same time, it shortens the stay in the ICU and in hospital.344,345 Remifentanil in turn has been shown to reduce the levels of biochemical markers of myocardial damage after coronary surgery, the duration of MV, and the length of hospital stay.346,347

It is now known that the adequate combination of short-acting sedating agents can reduce the analgesic needs and the adverse effects of long-acting opioids.322

Different protocols have evaluated the efficacy of the combination of propofol with midazolam, and of propofol with fentanyl.

The combination of low doses of propofol and midazolam has received widespread acceptance, since these drug substances exert a synergic effect by acting upon the same γ-aminobutyric acid (GABA) receptor–thus affording greater hemodynamic stability than propofol used as sole agent.321 Moreover, the combination of these drugs has been found to be an effective and safe alternative among patients in the postoperative period of heart surgery, since it exerts only minimum effects upon arterial pressure.348

Propofol as single agent for sedation has not been found to be superior to midazolam, since it is not associated with significant shortening of the time to withdrawal of the endotracheal tube, a reduction in the incidence of reintubation, postoperative hypertension and hypotension, or in the patient requirements.349 Nevertheless, during the withdrawal of TI, when the patient is still sedated, the administration of propofol is safe and reduces the incidence of hemodynamic alterations and myocardial ischemia.

No differences have been found in the duration of the awakening period or in sedation time on comparing propofol as single agent versus the combination propofol-fentanyl. However, the concentration of propofol, the infusion rate, and the total dose were all higher in the group in which propofol was used as only drug. Among the hemodynamic parameters, the drop in mean arterial pressure (over 20%) was greater in the group in which propofol was used as only drug than in the propofol-fentanyl group. Therefore, the combination of propofol-fentanyl is superior in terms of sedation, especially in preventing periods of hypotension in patients during the postoperative period.210,343

H7. Dexmedetomidine is recommended among patients in the postoperative period of cardiovascular surgery, either as single drug or combined with opioid analgesics.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: The characteristics of dexmedetomidine, which have already been commented above, define it as an appropriate option for short-action sedoanalgesia. In patients recovering from heart surgery, dexmedetomidine affords effective sedoanalgesia. In a clinical trial involving 89 patients subjected to prolonged coronary surgery, dexmedetomidine at a loading dose of 1μg/kg, followed by 0.4μg/kg/h and propofol 5μg/kg/h showed similar efficacy in sedoanalgesia.41,344,345,350–353 The prevention of postoperative trembling is an additional benefit of dexmedetomidine.354,355

H8. The use of pregabalin is recommended in elderly patients, since it reduces the need for opioids.

Grade of recommendation: weak. Level of evidence: moderate (2B).

Justification: A randomized, double-blind, controlled clinical trial on the effect of pregabalin upon the consumption of oxycodone, postoperative confusion and pain in 60 patients ≥75 years of age subjected to heart surgery found the use of pregabalin to reduce the postoperative consumption of oxycodone before extubation and in the first 24h after extubation from 16 to 9mg (p<0.001). Likewise, it reduced the incidence of confusion only on the first postoperative day (CAM-ICU in the pregabalin group 21 versus 24 in the placebo group [p=0.04]), though it increased the extubation time (10.6h) compared with the patients given placebo (8.3h).356

Fig. 6 details the management of patients in the postoperative period of cardiovascular surgery.

Figure 6.

Algorithm for analgesia and sedation in patients in the postoperative period of cardiovascular surgery. NSAIDs: nonsteroidal antiinflammatory drugs; TI: tracheal intubation; PCA: patient-controlled analgesia.

(0.47MB).

What medical considerations should be made before starting any type of sedation and analgesia?

I1. An initial neurological evaluation based on the clinical manifestations is recommended, with exclusion of the presence of space-occupying lesions or hematomas that can be surgically resolved, and adopting a local protocol or guide for the management of these patients.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: As in other patients admitted to the ICU, sedoanalgesia in neurocritical patients must seek to control or reduce the metabolic response to stress (tachycardia, hypertension, increased protein catabolism, etc.), maintain patient synchronization with the ventilator, and lessen the pain, anxiety, and agitation.357–359

However, some specific considerations apply in the neurocritical patient with central nervous system alterations due to brain injury or other CNS lesions, including the prevention of situations capable of increasing intracranial pressure (ICP); the reduction and maintenance of brain metabolic needs; elevation of oxygen uptake; optimization of systemic hemodynamics; and reduction of the brain metabolic oxygen demands.358–361 To this effect the following is required: (a) patient monitorization of the systemic and cerebral hemodynamic effects such as systemic arterial pressure, central venous pressure (CVP) and ICP; (b) follow-up of sedation using adequate scales that prove easy to use in clinical practice and are reproducible and widely accepted; and (c) protocolization and standardization of medical care.

When performing sedoanalgesia in neurocritical patients we must take into account that: (a) it must not interfere with continuous neurological assessment in the first hours, in order to be able to detect treatable intracranial complications requiring prompt intervention, and which can manifest as agitation or discomfort and (b) we must prevent secondary neurological damage, associated to hypoxemia and hypotension, which should be corrected as quickly as possible.358,360,362

Some deleterious systemic factors must be corrected or prevented before starting sedation, such as systemic arterial hypotension (maintaining a systolic blood pressure of over 90mmHg, with an ICP of 70mmHg), hypoxemia, fever or hypothermia and hyperglycemia.358–360

Which drugs are indicated when frequent evaluations of the patient neurological condition are required?

I2. It is advisable to use drugs with a short half-life and scant accumulation (propofol, dexmedetomidine and remifentanil), allowing frequent neurological evaluations. A sedation regimen based on analgesia with short-acting opioids such as remifentanil is indicated, since it allows adequate evaluation of the neurological condition and rapid awakening once the medication is suspended.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: The ideal sedative in the neurocritical patient is a drug that can prevent ICP elevations, keep the patient hemodynamically stable, and avoid deep sedation (rapid effect and short action). No single ideal agent is able to offer these properties, however, and a combination of different drugs is therefore needed in order to achieve the desired effects. Benzodiazepines are still used associated to analgesics, including particularly the morphine derivates.357 The use of hypnotics such as propofol in combination with an opioid like remifentanil is considered adequate for these patients, in which daily or more frequent interruption of sedation is essential.284,363

Propofol, in the same way as other barbiturates, reduces cerebral blood flow and oxygen consumption by up to 40–60%, in proportion to the administered dose. Furthermore, the drug exerts a vasoconstrictor effect upon the cerebral vascular system. When administered at sufficient doses to produce coma, its antiepileptic activity is comparable to that of the barbiturates, reducing ICP and, as an adverse effect, reducing cerebral perfusion pressure secondary to systemic hypotension, particularly in hypovolemic patients. The pharmacokinetic properties of propofol therefore allow it to be recommended as an ideal hypnotic agent in both the induction and maintenance of sedation in neurocritical patients, even in the management of intracranial hypertension, due to its easy titration and the rapid reversibility of the effect once infusion is suspended. These properties allow propofol to produce predictable sedation. Other potentially beneficial properties in patients with brain injuries are inhibition of the GABA system and the N-methyl-d-aspartate (NMDA) receptors, and the antioxidant effect of the drug.303,364

Opioids are the first choice for analgesia. These drugs should be used to reduce anxiety, pain and distress. The opioids in general do not exert important effects upon brain oxygen consumption. At analgesic doses, the hemodynamic, respiratory and neurological actions of the four derivatives (fentanyl, alfentanil, sufentanil and remifentanil) are comparable. The choice among them should be based on their respective pharmacodynamic characteristics. In patients with brain injuries it has been seen that the administration of opioids can reduce the cerebral perfusion pressure secondary to a reduction in mean arterial pressure and an increase in ICP. This effect has been described when the drugs are administered in bolus form, not as a continuous infusion.46

Sedation based on analgesia (remifentanil with the addition of boluses of propofol and midazolam) allows daily evaluation and faster awakening compared with the classical scheme (fentanyl or morphine, with the combination of propofol or midazolam).242,284 Remifentanil offers a concrete advantage in the neurocritical patient, since its pharmacokinetic profile ensures fast awakening once the medication is suspended–this in turn facilitating evaluation of the neurological condition of the patient.242 Morphine was one of the most widely used analgesics. However, its use is limited by slow onset of action (20min on average), the risk of accumulation in the presence of renal failure, and histamine release. As a result, the use of short-acting opioids such as remifentanil is presently preferred.284,365

No studies are available demonstrating the superiority of remifentanil versus other opioids in terms of a decrease in mortality rate, though remifentanil does offer advantages in terms of a shorter duration of hospital stay, a shorter duration of MV, and a shorter time to extubation. An inconvenience of remifentanil is the hyperalgesia produced when the drug is suspended, making it necessary to prescribe transition analgesics.

Table 12 details the properties of the above described drug substances.

Which sedative is advised for patients with intracranial hypertension and subjected to MV?

I3. The use of propofol in infusion is recommended, without exceeding 5mg/kg/h and a duration of 5 days. Midazolam should be considered in patients in which propofol is contraindicated.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: As commented above, propofol and midazolam are equally effective in sedation of the neurocritical patient, in accordance with their systemic and cerebral hemodynamic effects.284,364,366

I4. Thiopental sodium is recommended as a treatment measure reserved for patients with serious brain injuries presenting intracranial hypertension refractory to medical treatment and without coexisting major hemodynamic limitations.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: Barbiturates reduce blood flow to the brain and cerebral metabolism in direct proportion to the administered dose, until brain activity is ultimately abolished. The decrease in ICP is secondary to the effect of the drug upon cerebral perfusion, and in turn results from lowered brain metabolism, provided cerebral hemodynamics and the coupling of cerebral blood flow/oxygen consumption are maintained. If oxygen consumption decreases as a consequence of ischemic alterations or secondary neurological damage, the barbiturates increase blood flow through a compensatory mechanism, provided the systemic arterial pressure is maintained above the values determined by the autoregulatory mechanisms (mean arterial pressure over 90mmHg). However, it is important to remember that in addition to affecting the hemodynamic situation, barbiturates also cause immunosuppression and a prolongation of coma once their administration is suspended, due to drug redistribution in the adipose compartments.367–371

I5. It is not advisable to systematically use ketamine in patients with brain injuries or other neurocritical conditions.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: Ketamine is a non-competitive NMDA receptor antagonist with a primary action site located in the cortical neothalamus. Ketamine has been related to an increase in partial CO2 pressure in arterial blood and in ICP in patients without MV. However, it recently has been described that in patients with intracranial hypertension and controlled MV, ketamine in continuous infusion and midazolam maintain cerebral hemodynamics and control of brain perfusion to a degree comparable to that of the opioids.372 Certain adverse effects such as an increase in heart rate and longer neurological recovery after suspension (related to the presence of an active metabolite: norketamine) advise against the use of ketamine in neurocritical patients when frequent neurological evaluations are needed.

Which medical conditions should be evaluated before starting any type of sedation and analgesia?

J1. Evaluation of liver and kidney function is recommended in all patients requiring sedoanalgesia in the ICU.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: The clinical usefulness of most hypnotics, sedatives and analgesics is negatively affected by liver or renal failure, or (in the worst of cases) both.3 Failure of such organ function poses a genuine challenge for clinicians, and requires constant weighing of the risk–benefit ratio of the treatment provided, often without the support of adequate scientific evidence.373 Liver or renal failure produces changes not only in reference to clearance, distribution volume, free fraction or elimination of the original drug substance, but can also result in the accumulation of active metabolites, whether toxic or otherwise.

In the presence of liver dysfunction, most drug substances experience diminished clearance, a prolongation of the half-life, and the accumulation of metabolites that are potentially toxic or possess metabolic activity–with poorly known clinical repercussions. Experimental studies have shown that opioidergic transmission can be altered in cirrhotic patients, with an increase in receptor affinity for opioids. Furthermore, these patients show increased sensitivity to GABA, with reinforcement of the effects of benzodiazepines. Some forms of subclinical encephalopathy can be induced by the administration of sedatives and opioids. In patients with liver failure, the Child–Pugh classification374,375 is used as a guide in choosing the drug and in defining the dosage3,373,376–379 (Table 13).

J2. Evaluation of the risk–benefit ratio of sedoanalgesia in patients with chronic renal failure is recommended.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: In patients with chronic renal failure, whether on dialysis or not, the prediction of the pharmacokinetic profiles using formulas to calculate the glomerular filtration rate (GFR) has not been established for most drugs. In this context, most drug substances have not been extensively studied prior to their use in clinical practice in critical patients.373,380–382 Due to the changes in drug clearance and the potential accumulation of active metabolites, the clinician must evaluate the risk–benefit ratio taking into consideration other pharmacokinetic and pharmacodynamic interaction factors, as well as the potential adverse effects.

Which analgesics and sedatives are contraindicated, and why, in patients of this kind?

Which drugs are indicated for these procedures?

K1. An opioid analgesic, fentanyl or remifentanil, associated to a sedative (propofol, midazolam) is advised for these special procedures. The doses are to be modified taking into account the previous use of other sedatives and analgesics.

Grade of recommendation: weak. Level of evidence: low (2C).

K2. Protocolized opioid use is recommended in case of painful or unpleasant routine procedures (endotracheal suction and changes in body position).

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: No drug or drug combination has been adequately evaluated for anesthesia or analgesia in special procedures in the ICU. In the case of minor procedures carried out in the ICU, the sedatives, hypnotics or analgesics administered to the patient before performing the procedure must be taken into account. Among the alternatives, we can consider nerve blocks or infiltrations of local anesthetics, or may administer boluses equivalent to 25–50% of the basal opioid dose which the patient is receiving. When brief sedation is expected (<24h), propofol in bolus form is indicated. If sedation after the procedure is expected to last 48h or more, we should use midazolam or lorazepam as first choice.418–421

K3. The routine use of neuromuscular relaxants for performing special procedures in the ICU is not advised.

Grade of recommendation: weak. Level of evidence: low (2C).

Justification: Neuromuscular relaxants should only be used in special cases in which correct and safe performance of the procedure requires muscle relaxation (abdominal interventions, certain tracheostomies, fiberoptic bronchoscopy), or when the patient requires brain protective measures, as in intracranial hypertension.

When are regional analgesia techniques indicated for the management of pain in the ICU?

K4. Regional analgesia is recommended in the postoperative period of thoracotomy and major thoracoabdominal surgery, and in chest traumatisms.

Grade of recommendation: strong. Level of evidence: high (1A).

Justification: Regional analgesia can be useful in selected patients in the ICU for the management of chest injuries (multiple rib fractures, sternal fracture and lung contusion), or postoperative pain in the context of chest surgery and major thoracoabdominal interventions.422,423

Which regional analgesia technique is recommended for the management of pain in the ICU?

K5. The continuous peridural approach is recommended as the regional analgesia technique of choice in the postoperative period of thoracotomy, thoracoabdominal surgery and chest injuries. The paravertebral approach with continuous infusion is an alternative to the peridural route in the postoperative period of thoracotomy.

Grade of recommendation: strong. Level of evidence: high (1A).

Justification: The oldest and most widespread technique is peridural analgesia, which in comparison with intravenous analgesia using opioids in bolus doses or PCA, affords adequate analgesic control, facilitates respiratory physiotherapy, and reduces the duration of MV and the incidence of nosocomial pneumonia.422–424

The results of the trials that have compared the paravertebral technique versus the peridural approach indicate that both procedures offer similar analgesic potency, though with a lesser incidence of adverse effects such as hypotension, nausea, vomiting and urinary retention, when the paravertebral approach is used.425–428

K6. Intercostal block is suggested in the postoperative period of thoracotomy.

Grade of recommendation: weak. Level of evidence: moderate (2B).

Justification: Comparison of intercostal block versus peridural analgesia shows a decrease in opioid consumption (PCA) and in the incidence of urinary retention when the intercostal technique is used in programmed thoracotomy procedures.429

What should be done to modulate the external conditions that can affect patient tranquility, such as noise, waking-sleep, visits, inappropriate conversations?

L1. Sleep in the ICU is to be facilitated, adopting all the necessary measures, particularly non-pharmacological measures.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: Sleep is important for patient recovery. Objective and subjective measures of sleep quality in the ICU reveal the existence of important sleep disturbances. This in turn represents an additional source of stress that can have a negative impact upon the humoral and cellular immune system, with an increase in oxygen consumption and CO2 production, and alterations in thermoregulation.430,431

The causes of sleep disturbances among patients in the ICU include medical-nursing evaluations, diagnostic tests, noise, lights during the night, pain, discomfort and invasive procedures.432–434

Complementary measures can be used to facilitate sleep,435 such as the control of environmental illumination, massages, music therapy,436 the synchronization of activities with the circadian rhythm, and the lessening of noise.437 Nursing assessment or the use of a scale for sleep control is also important.438

L2. It is advisable to adopt all necessary measures to reduce noise in the ICU. As a complementary measure we can use earplugs to lessen noise perception.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: Noise in the ICU creates a hostile environment for the patient, producing sleep disturbances and anxiety.431–434,437,439–441 Noise in the ICU is produced by alarms, mechanical ventilators, telephones and conversations among the personnel members. Levels above 80dB are to be avoided, while levels below 35dB favor sleep.442 As a complementary measure we can use earplugs to lessen noise perception on the part of the patient.3,191,431,443,444

L3. As far as possible, it is advisable to observe the waking-sleep rhythm, lowering the lights at night, and reducing the nursing interventions or procedures.

Grade of recommendation: strong. Level of evidence: strong (1B).

Justification: The waking-sleep rhythm should be observed as far as possible, attempting to minimize sleep disturbances at night attributable to procedures, and affording an environment with the least illumination possible. A guide promoting the control of noise and lights at night in the ICU should be used.445,446

When and what relaxation and massage techniques can be used?

L4. Massages can be used as an alternative or adjuvant to drug treatment.

Grade of recommendation: strong. Level of evidence: weak (1C).

Justification: Back massaging for an average of 5–10min promotes relaxation and improves sleep,447 in the same way as foot massage applied for 5min.448 The combination of massages with acupressure has shown the same benefits.449

When should music therapy be used?

L5. Music therapy is recommended in patients admitted to the ICU, especially in those subjected to MV.

Grade of recommendation: strong. Level of evidence: moderate (1B).

Justification: Music therapy can help relax and lessen the pain in patients in the ICU. Music can also mask noise. In the postoperative period of heart surgery, listening to music during the first day has been associated with a decrease in discomfort produced by noise, as well as a drop in heart rate and systolic blood pressure.450 A similar effect has been documented in cancer patients admitted to the ICU.451 In patients subjected to MV, music therapy is associated with a decrease in anxiety, systolic and diastolic blood pressure, and heart rate.281,452–457 Nevertheless, larger studies are needed in order to confirm that music therapy is effective in all groups of patients. Since music therapy is an intervention without adverse effects and has a low cost, it should be considered among the measures for controlling anxiety and noise in the ICU.280–282,458–461

L6. It is advisable to inform the patient about his or her illness and the procedures to be carried out.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: The lack of information, or the inadequate management of the information which the patient receives, can contribute to increase anxiety.462 No adequate studies have been carried out on the appropriate way to inform patients in the ICU. Having a better understanding of their illness and of the interventions carried out can improve patient collaboration and lessen anxiety. Likewise, it seems reasonable to avoid inappropriate conversations among the medical or nursing personnel that may be heard by the patients.463,464

L7. It is advisable to establish an effective means of communication with patients subjected to MV.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: Patients who are subjected to MV and are not sedated or are under cooperative sedation, are better able to communicate with the attending healthcare personnel and with their relatives; as a result, they are better able to assess their condition and experience greater autonomy and wellbeing. Some recommended communication methods are gestures, movements of the head, writing, letter cards, words, phrases and images, and even electronic devices. In patients subjected to tracheostomy, we should consider the possibility of deflating the cuff to allow speech.465,466

L8. It is advisable to encourage the use of devices allowing patient orientation in the intensive care environment, such as wall clocks, calendars, windows with natural light, photos of relatives in visible places within the ICU, and patient personal items or objects of daily use.

Grade of recommendation: strong. Level of evidence: low (1C).

Justification: The presence of a clock, calendar, wall boards and similar objects allowing patients and their relatives to personalize the room, together with good wish cards, photos and other personal items, all create a comfortable environment for patient recovery. The room may even be equipped with television and an education/training system that can be used in support of the patient educational objectives and for providing entertainment.467

As a summary, Appendix C suggests a bundle of measures for the management of analgesia, sedation and delirium in the critical adult patient.

The members of the consensus group declare the following conflicts of interest: G. Castorena is a speech representative of MSD for Sugamadex; J.C. Díaz is a speech representative of Hospira; A. Hernández organizes academic meetings for Hospira and Boehringer Ingelheim; T. Muñoz is a consultant (Advisory Board) for Orion Pharma S.L.; F. Pálizas is a speech representative of Bayer for rivaroxaban and receives support for attending congresses on sepsis; J.M. Pardo receives support for attending congresses from MSD and Sanofi-Aventis; C. Righy is a speech representative of Hospira; M. Suárez is a speech representative of Hospira and receives support for attending congresses from Victus Laboratories and Abbot Laboratories. The rest declare that they have no conflicts of interest.