|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Neuromuscular blocking drugs are frequently used in conjunction with sedatives and analgesics in the ICU. Indications for the use of neuromuscular blockers in the ICU are outlined in Table 13-17 . Few data support their use, and evidence for a beneficial effect on pulmonary function or patient oxygenation is inconclusive.[755] [756] [757] [758] Nonetheless, nondepolarizing neuromuscular blockers are commonly used for weeks in ICU patients, most of the time without monitoring and frequently at doses exceeding those used in the operating room.[759] [760] The results of two surveys in the United States, including anesthesiologists and nurses with special certificates of competence in critical care, indicate that 98% of those surveyed use neuromuscular blocking drugs at least occasionally.[759] [760]
| Facilitate mechanical ventilation |
| Facilitation of endotracheal intubation |
| Enable patient to tolerate mechanical ventilation |
| High pulmonary inflation pressures, e.g., acute respiratory distress syndrome |
| Hyperventilation for increased intracranial pressure |
| Facilitate therapeutic or diagnostic procedures |
| Tetanus |
| Status epilepticus |
| Reduce oxygen consumption |
| Abolish shivering |
| Reduce work of breathing |
Of particular concern in intensive care settings is the risk of paralyzed patients receiving inadequate analgesia and sedation.[761] [762] [763] This may be due to the fact that ICU nurses and physicians are unfamiliar with the pharmacology of the neuromuscular blocking drugs.[759] [762] For instance, pancuronium was thought to be an anxiolytic by 50% to 70% of ICU nurses and house staff, and 5% to 10% thought that it was an analgesic.[762] In the United Kingdom, the erroneous use of neuromuscular blockers as sedatives in intensive care was not uncommon in the 1980s.[764] [765] [766] Approximately 96% of ICU patients received neuromuscular blockers to aid mechanical ventilation in 1980. By 1986, their use had fallen to 16% of ventilated patients.[764] [765] [766] This marked reduction followed the publication of patients' ordeals who were paralyzed while conscious in the ICU.[15] In the United States, neuromuscular blockers are used in less than 20% of all patients requiring mechanical ventilation.[759]
Prolonged ICU stay during critical illness is associated with disorders of neuromuscular function that contribute to morbidity, increased length of hospital stay, weaning difficulties, and prolonged rehabilitation.[767] [768] Complications of long-term administration of neuromuscular blockers in the ICU are outlined in Table 13-18 . In the ICU, the duration of mechanical ventilation, sepsis, dysfunction of two or more organs, female gender, administration of steroids, and hypercapnia are known risk factors for neuromuscular dysfunction.[769] [770] [771] Syndromes of weakness in critically ill patients are relatively common and probably polymorphic in origin. In a retrospective study of 92 critically ill patients with clinically diagnosed weakness, electromyographic studies indicated that acute myopathy (critical illness myopathy) is three times as common as acute axonal neuropathy (critical illness neuropathy) (43% versus 13%, respectively).[767] The additional health care cost of one case of persistent weakness was estimated to be approximately $67,000.[772] The differential diagnosis of neuromuscular weakness in the ICU is listed in Table 13-19 .
Lacomis and colleagues[773]
suggested
using the term "critical illness myopathy" (CIM) instead of the current terminology
used in the literature such as acute quadriplegic myopathy,[774]
acute (necrotizing) myopathy of
| Short-term use |
| Specific, known drug side effects |
| Inadequate ventilation in the event of ventilator failure or circuit disconnection |
| Inadequate analgesia and/or sedation |
| Long-term use |
| Complications of immobility |
| Deep venous thrombosis and pulmonary embolism |
| Peripheral nerve injuries |
| Decubitus ulcers |
| Inability to cough |
| Retention of secretions and atelectasis |
| Pulmonary infection |
| Dysregulation of nicotinic acetylcholine receptors |
| Prolonged paralysis after stopping relaxant |
| Persistent neuromuscular blockade |
| Critical illness myopathy |
| Critical illness polyneuropathy |
| Combination of the above |
| Unrecognized effects of drug or metabolites |
| Succinylcholine and metabolic acidosis/hypovolemia |
| 3-Desacetylvecuronium and neuromuscular blockade |
| Laudanosine and cerebral excitation |
Most published reports of CIM in the ICU have focused on patients with status asthmaticus.[777] [778] [779] Affected individuals have typically been treated with corticosteroids and nondepolarizing neuromuscular blockers. Nevertheless, myopathy has also been documented in asthmatic patients, in those with chronic lung disease without paralysis who received corticosteroids,[780] [781] and in critically ill patients with sepsis who received neither corticosteroids nor nondepolarizing neuromuscular blockers. [782] [783] Animal studies found that the number of cytosolic corticosteroid receptors is increased in immobilized muscles relative to contralateral controls.[784] It seems—at least in some patients—that prolonged immobility may be the key risk factor for myopathy in corticosteroid-treated patients[785] and that selective muscle atrophy is a result of changes in glucocorticoid sensitivity. [784]
Sepsis, immobility, and the catabolism associated with negative nitrogen balance may also result in myopathy.[17] [768] Skeletal muscle hypoperfusion is noted in patients with severe sepsis despite normal or elevated whole blood oxygen delivery. [786] Antibodies to nAChRs have been demonstrated in a rodent model of sepsis.[787] This myasthenialike syndrome is also seen in critically ill patients. Evidence of local immune activation by cytokine expression in skeletal muscles was reported in patients with CIM.[788]
The major feature of CIM is flaccid weakness that tends to be diffuse and often includes the facial muscles and the diaphragm.[773] The clinical features of CIM overlap with those of critical illness polyneuropathy (CIP) and prolonged neuromuscular blockade.[773] Electrophysiologic studies and increases in serum creatine kinase concentrations
| Central nervous system |
| Septic or toxic-metabolic encephalopathy |
| Brainstem stroke |
| Central pontine myelinolysis |
| Anterior horn cell disorders (e.g., amyotrophic lateral sclerosis) |
| Peripheral neuropathies |
| Critical illness polyneuropathy |
| Guillain-Barré syndrome |
| Porphyria |
| Paraneoplastic |
| Vasculitis |
| Nutritional and toxic |
| Neuromuscular junction disorders |
| Myasthenia gravis |
| Lambert-Eaton myasthenic syndrome |
| Botulism |
| Prolonged neuromuscular junction blockade |
| Myopathies |
| Critical illness myopathy |
| Cachectic myopathy |
| Rhabdomyolysis |
| Inflammatory and infectious myopathies |
| Muscular dystrophies |
| Toxic |
| Acid maltase deficiency |
| Mitochondrial |
| Hypokalemia |
| Hypermetabolic syndromes with rhabdomyolysis (e.g., neuroleptic malignant syndrome) |
| From Lacomis D: Critical illness myopathy. Curr Rheumatol Rep 4:403–408, 2002. |
The polyneuropathy seen in the critically ill has been termed critical illness polyneuropathy. CIP affects both sensory and motor nerves and occurs in 50% to 70% of patients with multisystem organ failure and systemic inflammatory response syndrome (SIRS).[789] [790] [791] [792] It has been postulated that SIRS contributes to CIP by releasing cytokines and free radicals that damage the microcirculation of the central and peripheral nervous systems.[788] [781] Dysregulation of the microcirculation may render the peripheral nervous system susceptible to injury.[793]
No specific treatment is available for weakness syndromes in critically ill patients other than physical rehabilitation. Intravenous immunoglobulin and nerve growth factors appear to be promising in CIP syndrome.[794] [795] Recently, intensive insulin therapy during critical illness has been found to decrease the risk of CIP.[796] [797] Maintenance of blood glucose at or below 110 mg/mL in critically ill patients may reduce the risk of CIP.[796] [797]
The outcomes from CIM and CIP appear to be similar.[767] The reported mortality rate of patients with CIP syndrome is about 35%.[798] In one study, 100% of the patients (13 of 13) who survived had abnormal clinical or neurophysiologic findings 1 to 2 years after the onset of CIP syndrome.[799] The quality of life was markedly impaired in all patients.[799]
It is likely that upregulation of nAChRs induced by immobilization and by prolonged administration of nondepolarizing neuromuscular blockers[800] [801] [802] contributes to (1) the higher incidence of cardiac arrest associated with the use of succinylcholine in ICU patients[803] [804] and (2) the increased requirements for nondepolarizing neuromuscular blockers in ICU patients.[802] [805] [806] [807] Upregulation of nAChRs was noted in the muscles of deceased critically ill adults who had received long-term infusions of vecuronium.[803] Therefore, succinylcholine is best avoided in ICU patients when total-body immobilization exceeds 24 hours.[17] In a recent survey in U.K. ICUs, 68.7% of the respondents indicated that they would use succinylcholine in a clinical scenario suggestive of CIP.[808] This result highlights the lack of awareness of the dangers associated with the use of succinylcholine in these patients.[808]
Nondepolarizing neuromuscular blocker-associated persistent weakness appears to be a distinct pathologic entity and is not simply a manifestation of weakness syndromes in the critically ill.[789] A prospective study by Kupfer and associates[809] showed a 70% incidence of persistent weakness in ICU patients who received neuromuscular blockers for more than 2 days versus a 0% incidence in similar ICU patients who received no neuromuscular blocker. This study is compelling evidence for the role of nondepolarizing neuromuscular blockers in this complication.
Long-term weakness has been described after all commonly used nondepolarizing neuromuscular blockers.[305] [777] [779] [810] [811] The overall incidence of prolonged paralysis after long-term use of neuromuscular blockers is about 5%. Approximately 20% of patients who received neuromuscular blockers for more than 6 days,[810] 15% to 40% of asthmatic patients who also received high-dose steroids,[776] [778] and 50% of patients with renal failure who received vecuronium suffered prolonged weakness.[305] Clinically, it appears that prolonged recovery from neuromuscular blockade occurs more frequently when steroidal neuromuscular blockers are used.[305] [810]
However, prolonged weakness was also noted after the use of atracurium in ICU patients.[811] Furthermore, the use of atracurium has raised concern regarding its metabolite laudanosine. Laudanosine is also detected in the cerebrospinal fluid (CSF) of ICU patients who receive atracurium.[812] It is an analeptic and can trigger seizures in animals.[813] The toxic dose in humans is not known, but case reports have described patients having seizures while receiving atracurium, and laudanosine has not been
Nondepolarizing neuromuscular blockers are polar molecules and do not readily cross the blood-brain barrier, but vecuronium and its long-acting active metabolite (3-desacetylvecuronium) have been detected in the CSF of patients in the ICU. The CNS effects of neuromuscular blockers and their metabolites in humans have not been well studied, but in rats, atracurium, pancuronium, and vecuronium injected into the CSF will cause dose-related cerebral excitation culminating in seizures.[813] Cerebral excitation with consequent increased cerebral oxygen demand is undesirable in ICU patients at risk for cerebral ischemia. It has also been suggested that nondepolarizing neuromuscular blockers can gain access to nerves during SIRS and directly result in neurotoxicity.[793] [813] [820]
Combining corticosteroids and nondepolarizing neuromuscular blockers
should be avoided.[821]
When nondepolarizing neuromuscular
blockers are necessary, the use of a peripheral nerve stimulator is recommended,
and periodic return of muscle function should be allowed. However, routine monitoring
of neuromuscular function alone is not sufficient to eliminate prolonged recovery
and weakness syndromes in ICU patients.[822]
Adjusting
the dosage of neuromuscular blockers by peripheral nerve stimulation versus standard
clinical dosing in critically ill patients reduces drug requirements, produces faster
recovery of neuromuscular function, and results in a total cost savings of $738 per
patient.[823]
A recent study found that daily interruption
of sedative drug infusions decreases the duration of mechanical ventilation and length
of stay in the ICU.[824]
The impact of such an
approach on the weakness syndromes in ICU patients is unknown. When nondepolarizing
neuromuscular blockers are used, the guidelines in Table
13-20
may help
| Avoid the use of neuromuscular blockers by |
| Maximal use of analgesics and sedatives |
| Manipulation of ventilatory parameters and modes |
| Minimize the dose of neuromuscular blockers |
| Use a peripheral nerve stimulator with train-of-four monitoring |
| Do not administer for more than 2 days continuously |
| Administer by bolus rather than infusion |
| Administer only when required and to achieve a well-defined goal |
| Continually allow recovery from paralysis |
| Consider alternative therapies |
| Avoid vecuronium in female patients with renal failure |
| Use isoflurane in place of muscle relaxants in severe asthmatics |
| Minimize the dose of steroid in asthmatics |
|
|
|
|
|
|
|
|
|
|
|
|
|
