Extremely prolonged neuromuscular block after cardiopulmonary resuscitation

A young woman known with end-stage heart failure and renal and liver abnormalities underwent cardiopulmonary resuscitation. seven hours after administration of 1.2mg/kg of rocuronium, acceleromyography still showed a complete neuromuscular block. After administration of rocuronium-antagonist sugammadex (16mg/kg), she could promptly move upon commands. several of the published risk factors for block prolongation were present in our patient. To our knowledge, this is the first time that sugammadex reversed an extremely prolonged rocuronium-induced neuromuscular block. This case underscores the importance of recognizing neuromuscular block prolongation in ICU patients. In such instances testing for the presence of residual paralysis and the administration of sugammadex as a novel direct antagonist for rocuronium should be considered. keywords rocuronium, prolonged neuromuscular block, suggamadex, acceleromyography, TOF, Coma, post resuscitation Case description The patient was a 32-year old woman (weight 86 kg, height 154 cm; BMI 36) who presented to our hospital because of suspected catheter-related infection. The patient had been known to us for 10 years with a post-partum dilated heart failure. she had recently been admitted to the cardiology ward for screening for heart transplantation. During this admission mild liver function abnormalities were noted. subsequently, a subcutaneous tunnelled subclavian vein catheter was placed for long-term inotropic support with dobutamine. Liver function tests had normalized when the patient was discharged with a continuous dobutamine infusion at 2ug/kg/min. After one week she was readmitted to the coronary care unit (CCU) with malaise and suspected catheter-related infection that was treated by catheter replacement and administration of vancomycin. Despite conservative measures, her renal function deteriorated rapidly with an estimated glomerular filtration rate of 12 ml/min (creatinine 365 μmol/l) During the morning rounds on the CCU the patient collapsed whilst in the middle of a conversation. Immediate resuscitation (witnessed pulseless electrical activity) according to the resuscitation guidelines was started. The patient was intubated after administration of a single dose 1.2 mg/kg (100 mg) of the neuromuscular blocking (NMB) agent rocuronium to facilitate opening the mouth to release a strong bite. During the prolonged resuscitation (3 hours) the intra-arterial blood pressures were equal or higher than her normal pressure under inotropic support. A total of 10mg of adrenalin and 20 IU of vasopressin were administered. On admission to the ICU, the patient was unresponsive with dilated pupils and no light reflexes. she received continuous infusion of adrenalin, noradrenalin, dopamine and levosimendan for persisting cardiogenic shock. This severe haemodynamic instability was the main reason for not inducing therapeutic hypothermia. A continuous infusion of 4 gram magnesium sulphate per day was also started. Both on admission to the ICU and seven hours after the single dose of rocuronium, examination by two neurologists revealed a Glasgow Coma score (GCs; eyemotor-verbal) of 1-1-tube with no brain stem reflexes. However, at seven hours after resuscitation she was able to trigger the ventilator, probably because the diaphragm recovers more rapidly from NMB activity than the ulnar nerve and thumb, and because only a slight contraction of the diaphragm is enough to trigger a ventilator. since renal insufficiency may prolong neuromuscular blockage even for rocuronium, acceleromyography (TOFWatch® (Organon Teknika, Boxtel, Holland)) in a train-of-four (TOF) mode with the use of supramaximal stimuli (60mA) with a duration of 0.2ms at 2 Hz every 15s was obtained. It revealed a complete neuromuscular block (TOF-0) at several stimulation sites (ulnar, facial and tibial nerves). The device was checked for technical malfunction on the examiner’s ulnar nerve at a low mA output. since it was unclear to what extent the neuromuscular block was contributing to the patient’s low GCs, a single dose of sugammadex 16mg/kg (dose for complete block reversal) was administered. sugammadex antagonizes rocuronium by encapsulating the rocuronium molecule, after which the complex is excreted in the urine. If adequately dosed, sugammadex is capable of rapidly reversing a complete rocuronium-induced block, even in patients with end-stage renal failure [1,2]. Within 2 minutes of receiving the sugammadex, the patient became fully responsive with a GCs of 4-6-tube. We concluded that the patient had not experienced a true coma but had been paralyzed. The presence of cardiac failure, renal failure and knowledge of the pharmacokinetics of rocuronium provided the necessary clue for performing acceleromyography in this patient. MWN Nijsten E-mail: m.w.n.nijsten@icv.umcg.nl Correspondence Extremely prolonged neuromuscular block after cardiopulmonary resuscitation Netherlands Journal of Critical Care NETH J CRIT CARE VOLUME 15 NO 5 OCTOBER 2011 250 AG stegeman, A Oude Lansink, F Ismael, BM de Jong, MW Nijsten Continuous renal replacement therapy was started to improve the metabolic acidosis but had no beneficial effect on the patient’s haemodynamics. For rapid haemodynamic improvement, the patient was taken to the operating room and fitted with a left ventricular assist device (LVAD Levitronix®). However, lactic acidosis persisted, repeated ventricular tachycardia developed and her internal cardioverter defibrillator was triggered several times. On the next day, sustained and refractory ventricular fibrillation occurred as a result of which the LVAD output declined sharply. Later that day, and 22 hours after the cardiopulmonary resuscitation had been started, the patient died. Her death was probably due to right heart failure rendering the LVAD ineffective as reflected by progressive lactic acidosis. Because this patient died, our Institutional Review Board has allowed publication of this case without informed consent having been obtained. discussion The fact that our patient displayed a complete neuromuscular block seven hours after the administration of 1.2 mg/kg of rocuronium is probably due to several factors, including a low cardiac output. The patient’s apparent comatose state associated with this block was immediately reversed after administering sugammadex. In the literature we found three cases that had a similar length of neuromuscular block prolongation [3,4]. However, these patients were all over 60 years of age and in one patient only was rocuronium the only neuromuscular blocker used. A case with a less extreme prolongation of blockage occurred with a dose of 0.6 mg/kg in an 84-year-old patient. In this case the T1 (first twitch 25% of maximal twitch height) response on TOF was obtained 193 minutes after the single intubation dose [5]. Rocuronium is an NMB of the non-depolarizing steroid type. With regard to onset, it is the fastest non-depolarizing NMB [6]. At a dose of 1.2 mg/kg, its mean onset time is 55 sec (range 36-84 sec). Rocuronium is frequently used as an alternative to the depolarizing agent succinylcholine since it does not induce a rise in potassium levels or increased intracranial pressure and since its elimination is not dependent on the function of plasma cholinesterase. In the lower dose range (0.6mg/kg) rocuronium has an intermediate duration of action and it is cleared by rapid redistribution from the neuromuscular junction. Rocuronium is mainly eliminated through the hepatobiliary pathway with a variable elimination through renal excretion (12-33%). The importance of the renal elimination route appears greater as the rocuronium dose increases [7,8]. By monitoring the depth of neuromuscular blockade, rocuronium can be titrated to the desired effect and unusual resistance or sensitivity detected. This can be done with an acceleromyography method such as the train-of-four (TOF). A motion sensor is placed on the thumb and two stimulation electrodes are placed on the skin over the ulnar nerve. After electrode stimulation, adduction of the thumb is measured, with the response before the administration of the NMB defined as 100%. TOF is frequently used in the evaluation of nondepolarizing block. A TOF ratio (T4/T1) of 75% is correlated with clinical recovery Multiple causes for the extreme prolongation of the neuromuscular block after a single rapid sequence dose of rocuronium in our young female patient may have been relevant (Table 1). A high BMI may result in relatively high doses in patients with a low lean body mass. The variation in duration of action of rocuronium in a mixed clinical population is significant, depending on multiple patient factors. Female patients have longer block durations: after a dose of 0.4 mg/kg, time to recovery to 90% of maximal twitch height was 47 minutes in females compared to 34 minutes in male patients [9]. In elderly patients after a 0.6 mg/kg intubation dose, the duration to T1 ranged from 33 to 119 minutes [10]. However, in contrast to the previously mentioned cases, our patient was a young female. The variability in block duration in young healthy patients is also considerable. The spontaneous recovery index of rocuronium versus cis-atracurium was assessed in young healthy adults under propofol anaesthesia, by measuring the time interval from T1-25% to TOF 90%. The variability of this index was twice as great for rocuronium compared to cis-atracurium [11]. The block duration of rocuronium is prolonged in patients with renal dysfunction. In young patients with propofol-based anaesthesia, block duration to T1 (25% height) of 0.6 mg/kg, rocuronium was 32.8 +/5.6 minutes in patients without renal failure versus 58.4 +/20.2 minutes for patients with renal failure [12]. This block prolongation in renal failure is accompanied by an even larger variability in recovery time. A recovery time of 88 minutes (range 45-150) was observed in patients with re