The Use of Neuromuscular Blocking Agents in the ICU
The Use of Neuromuscular Blocking Agents in the ICU
ALI/ARDS is managed by treating the underlying cause of respiratory failure while reducing the risk of ventilator-induced lung injury. Induction of paralysis may increase chest wall compliance, eliminate patient-ventilator dyssynchrony, facilitate lung recruitment, reduce inflammatory mediator release, decrease lung hyperinflation, and reduce oxygen consumption (albeit controversial). At least eight clinical trials have assessed the use of NMBAs for managing ALI/ARDS (Table 3). Two small observational trials in ALI/ARDS patients prior to the year 2000 reported no effect on oxygenation when using a pancuronium bolus. A large retrospective study by Arroliga et al in 2005 noted that 13% of patients were administered NMBAs for at least 1 day. NMBA use was associated with prolonged duration of mechanical ventilation, ICU length of stay, and an increase in mortality. A small randomized crossover trial in severe sepsis patients reported that oxygen consumption or delivery was not improved in patients randomized to receive NMBAs.
Short-term use of cisatracurium in patients with ALI/ARDS has been associated with beneficial outcomes. Two small randomized controlled trials using cisatracurium in patients with ARDS demonstrated an improvement in oxygenation. Another randomized trial in ARDS patients demonstrated that the early use of cisatracurium for 48 hours improved oxygenation and reduced concentrations of pulmonary inflammatory mediators. A larger multicenter trial in patients with severe ARDS (PaO2/FIO2 < 150 mm Hg) reported that early administration of cisatracurium for 48 hours increased adjusted 90-day survival, ventilator-free days, organ failure–free days, and reduced barotrauma. Further studies are required to define the appropriate combination of sedation and NMBAs and to identify when NMBA use will improve outcomes in patients with ALI/ARDS.
NMBAs are used sparingly for patients with status asthmaticus to minimize ventilator asynchrony, lung hyperinflation, and barotrauma.Table 4 presents several trials examining NMBA use in patients with status asthmaticus. ICU-AW is reported in this population and appears to be more commonly associated with the use of concomitant high-dose steroids. A recent retrospective study in mechanically ventilated patients with status asthmaticus suggested that patients who require deep sedation with persistent immobilization are still at risk for weakness, despite a decline in the duration of induced paralysis. The risk of prolonged weakness may be reduced by using the minimal doses of sedation, corticosteroids, and NMBAs required to achieve the desired effect and to withdraw these drugs as soon as possible.
NMBAs are typically reserved for patients with intracranial hypertension in whom sedation alone does not reduce ICP. Few studies have evaluated the use of NMBAs for the management of elevations in ICP due to coughing, suctioning, or movement (Table 5). Hsiang et al suggested that while NMBAs may reduce mortality, they may increase severe disability. The routine use of NMBAs for elevated ICP does not appear to be indicated at this time. Patients who receive extended neuromuscular blockade as a second tier therapy for elevated ICP can be monitored with peripheral nerve stimulation to potentially avoid unwanted side effects (see Monitoring section).
Intra-abdominal hypertension (IAH) is defined as a repeated elevation in IAP of at least 12 mm Hg. ACS is defined as continued IAH of greater than 20 mm Hg with end-organ dysfunction or failure. Reduced abdominal wall compliance due to third spaced fluids, tense abdominal closures, and pain or inadequate sedation can lead to further increases in IAPs and subsequent organ failure. NMBAs have been reported to improve elevated IAPs by reducing abdominal muscle tone.
Neuromuscular blockade may provide clinicians with more time to remove fluid or treat the underlying cause of IAH and avoid surgical decompression.Table 6 presents a few studies examining the use of NMBA in the treatment of IAH. A small prospective trial suggested that a bolus dose of cisatracurium was effective in significantly decreasing mild elevations in IAP. A recent case report describing a patient undergoing adrenalectomy who had ACS reported that a prolonged NMBA infusion of 48 hours was effective in reducing IAPs and providing a good recovery. It has been recommended (Grade 2C) by the International ACS Consensus Definitions Conference Committee that NMBAs can be used in selected patients to reduce mild-to-moderate elevations of IAP.
In 2002, two landmark trials demonstrated that using mild hypothermia (32–34° C) for 12–24 hours in unconscious patients after out-of-hospital VF cardiac arrest improved neurologic outcomes, with one trial suggesting a survival benefit. This therapy has been validated in other randomized studies and meta-analyses. NMBAs were primarily used to prevent shivering in the two original trials (and others).
The optimal combination of sedatives, analgesics, and paralytics during hypothermia after VF-associated cardiac arrest is unknown. Chamorro et al performed a systematic review of 44 studies (68 international ICUs, primarily European) examining intensivists' preferences for the administration of sedatives, analgesics, and NMBAs during therapeutic hypothermia after VF cardiac arrest. A significant variability in the protocolized use of all medications for these patients was found. Fifty-four ICUs routinely used NMBAs to prevent shivering, whereas eight ICUs used NMBAs to treat shivering. Pancuronium was the primary agent used in 24 international ICUs surveyed, whereas cisatracurium was the second most common agent used. A minority of ICUs used neuromuscular monitoring to guide NMBA dosing and therapy. Studies are required to elucidate the optimal type, dose, and mode of administration of NMBAs, as well as optimal combination of sedatives and analgesics in this patient population.
ALI/ARDS
ALI/ARDS is managed by treating the underlying cause of respiratory failure while reducing the risk of ventilator-induced lung injury. Induction of paralysis may increase chest wall compliance, eliminate patient-ventilator dyssynchrony, facilitate lung recruitment, reduce inflammatory mediator release, decrease lung hyperinflation, and reduce oxygen consumption (albeit controversial). At least eight clinical trials have assessed the use of NMBAs for managing ALI/ARDS (Table 3). Two small observational trials in ALI/ARDS patients prior to the year 2000 reported no effect on oxygenation when using a pancuronium bolus. A large retrospective study by Arroliga et al in 2005 noted that 13% of patients were administered NMBAs for at least 1 day. NMBA use was associated with prolonged duration of mechanical ventilation, ICU length of stay, and an increase in mortality. A small randomized crossover trial in severe sepsis patients reported that oxygen consumption or delivery was not improved in patients randomized to receive NMBAs.
Short-term use of cisatracurium in patients with ALI/ARDS has been associated with beneficial outcomes. Two small randomized controlled trials using cisatracurium in patients with ARDS demonstrated an improvement in oxygenation. Another randomized trial in ARDS patients demonstrated that the early use of cisatracurium for 48 hours improved oxygenation and reduced concentrations of pulmonary inflammatory mediators. A larger multicenter trial in patients with severe ARDS (PaO2/FIO2 < 150 mm Hg) reported that early administration of cisatracurium for 48 hours increased adjusted 90-day survival, ventilator-free days, organ failure–free days, and reduced barotrauma. Further studies are required to define the appropriate combination of sedation and NMBAs and to identify when NMBA use will improve outcomes in patients with ALI/ARDS.
Status Asthmaticus
NMBAs are used sparingly for patients with status asthmaticus to minimize ventilator asynchrony, lung hyperinflation, and barotrauma.Table 4 presents several trials examining NMBA use in patients with status asthmaticus. ICU-AW is reported in this population and appears to be more commonly associated with the use of concomitant high-dose steroids. A recent retrospective study in mechanically ventilated patients with status asthmaticus suggested that patients who require deep sedation with persistent immobilization are still at risk for weakness, despite a decline in the duration of induced paralysis. The risk of prolonged weakness may be reduced by using the minimal doses of sedation, corticosteroids, and NMBAs required to achieve the desired effect and to withdraw these drugs as soon as possible.
Increased ICP
NMBAs are typically reserved for patients with intracranial hypertension in whom sedation alone does not reduce ICP. Few studies have evaluated the use of NMBAs for the management of elevations in ICP due to coughing, suctioning, or movement (Table 5). Hsiang et al suggested that while NMBAs may reduce mortality, they may increase severe disability. The routine use of NMBAs for elevated ICP does not appear to be indicated at this time. Patients who receive extended neuromuscular blockade as a second tier therapy for elevated ICP can be monitored with peripheral nerve stimulation to potentially avoid unwanted side effects (see Monitoring section).
Increased IAP
Intra-abdominal hypertension (IAH) is defined as a repeated elevation in IAP of at least 12 mm Hg. ACS is defined as continued IAH of greater than 20 mm Hg with end-organ dysfunction or failure. Reduced abdominal wall compliance due to third spaced fluids, tense abdominal closures, and pain or inadequate sedation can lead to further increases in IAPs and subsequent organ failure. NMBAs have been reported to improve elevated IAPs by reducing abdominal muscle tone.
Neuromuscular blockade may provide clinicians with more time to remove fluid or treat the underlying cause of IAH and avoid surgical decompression.Table 6 presents a few studies examining the use of NMBA in the treatment of IAH. A small prospective trial suggested that a bolus dose of cisatracurium was effective in significantly decreasing mild elevations in IAP. A recent case report describing a patient undergoing adrenalectomy who had ACS reported that a prolonged NMBA infusion of 48 hours was effective in reducing IAPs and providing a good recovery. It has been recommended (Grade 2C) by the International ACS Consensus Definitions Conference Committee that NMBAs can be used in selected patients to reduce mild-to-moderate elevations of IAP.
Therapeutic Hypothermia After Out-of-Hospital VF-associated Cardiac Arrest
In 2002, two landmark trials demonstrated that using mild hypothermia (32–34° C) for 12–24 hours in unconscious patients after out-of-hospital VF cardiac arrest improved neurologic outcomes, with one trial suggesting a survival benefit. This therapy has been validated in other randomized studies and meta-analyses. NMBAs were primarily used to prevent shivering in the two original trials (and others).
The optimal combination of sedatives, analgesics, and paralytics during hypothermia after VF-associated cardiac arrest is unknown. Chamorro et al performed a systematic review of 44 studies (68 international ICUs, primarily European) examining intensivists' preferences for the administration of sedatives, analgesics, and NMBAs during therapeutic hypothermia after VF cardiac arrest. A significant variability in the protocolized use of all medications for these patients was found. Fifty-four ICUs routinely used NMBAs to prevent shivering, whereas eight ICUs used NMBAs to treat shivering. Pancuronium was the primary agent used in 24 international ICUs surveyed, whereas cisatracurium was the second most common agent used. A minority of ICUs used neuromuscular monitoring to guide NMBA dosing and therapy. Studies are required to elucidate the optimal type, dose, and mode of administration of NMBAs, as well as optimal combination of sedatives and analgesics in this patient population.
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