ABSTRACT & COMMENTARY
Synopsis: The problem of histamine release and its effect on cerebral hemodynamics by bolus injection of atracurium is overcome by switching to cisatracurium.
Source: Schramm WM, et al. Anesth Analg 1998;86(1): 123-127.
Occasionally, boluses of muscle relaxants are used to facilitate intubation or prevent rises in intracranial pressure (ICP) in neurologically injured patients. The choice of muscle relaxant is usually based on rapidity of onset, relaxation conditions required, anticipated side-effects, and organ failures. Atracurium is frequently selected due to its predictable metabolism despite liver or renal dysfunction.In neurologically impaired patients, however, there are two concerns with using atracurium-histamine release and production of laudanosine, a compound capable of producing seizures in animals. Cisatracurium is more potent, less likely to release histamine, and produces less laudanosine than atracurium. This study compared the hemodynamic effects of bolus injection of atracurium and cisatracurium in 14 sedated, unconscious, mechanically ventilated patients with neurologic injuries.
In a blinded, cross-over design, each patient received three times the intubating dose of atracurium (0.75 mg/kg) and cisatracurium (0.15mg/kg), and ICP, systemic hemodynamics, and middle cerebral artery blood flow velocity (CBFV) were recorded every minute for 15 minutes. Cerebral perfusion pressure (CPP) was calculated and changes expressed as percentages change from baseline. No changes in any variable were seen after the cisatracurium bolus. Atracurium decreased ICP, CPP, and CBFV in 2-4 minutes with a rebound in CBFV and ICP at 9-12 minutes. Five patients demonstrated histamine-type reactions with a fall in blood pressure and cutaneous flushing. When these patients were eliminated from the analysis, no changes in cerebral hemodynamics were seen after atracurium.
COMMENT BY CHARLES G. DURBIN, Jr., MD, FCCM
This study confirms the expected lack of systemic and cerebral hemodynamic effects of cisatracurium boluses in neurologically impaired patients. It also suggests but does not prove that histamine release is the mechanism by which atracurium's effects are mediated. The test conditions were well-controlled. Patients were mildly hyperventilated (PaCO2 32-40 mmHg) and were rendered unresponsive with infusions of sufentanil and midazolam. These treatments should produce stable cerebral vascular conditions and minimize the effects of the test drugs. In fact, the changes observed were modest and clinically insignificant, averaging less than a 15% change. No patient experienced profound effects, and none developed an ICP greater than 26 mmHg or a CPP less than 50 mmHg.The main concern with switching to cisatracurium is cost. Atracurium is soon to be off patent and will thus become much less expensive. Is reduced histamine release a significant benefit? Other methods for reducing the effects of atracurium on histamine release are available. Simply injecting the drug more slowly, over 45-60 seconds, reduces the hemodynamic effects of the released histamine. There is no problem with continuous infusions of atracurium. H-2 blockers substantially reduce the bolus drug effects as well. None of the patients in this study were receiving H-2 blockers. Most patients in neurologic critical care units would be expected to receive H-2 blockers for GI bleeding prophylaxis, making the concerns of using atracurium even less. Not all patients exhibited histamine release; only five of the 14 patients in this study exhibited changes.
The claim that cisatracurium produces less laudonasine is yet to be substantiated, and, even if true, no case of seizures from laudonasine in humans has been reported, even in the presence of renal failure which causes the accumulation of this metabolite.
There are significant advantages of atracurium over other relaxants in the ICU, whether the small improvement in safety of cisatracurium over atracurium justifies the cost difference remains to be established.