Patient's death as a result of mistakenly injection of pancuronium.

Pancuronium is a typical non-depolarizing, curare-mimetic, very potent muscle relaxant. Besides application in anesthesiology and intensive care, it is used in execution as a part of lethal injection. In medico-legal practice, there are cases of using this substance in order to commit suicide or to deprive other people of their lives. Accidental pancuronium intoxications are very rare. The authors present such case ended in sudden death of hospitalized woman after mistakenly injection of the drug. 57-year-old female alcoholic was admitted to the Acute Poisoning Centre after ethylene glycol ingestion. During the fifth day of treatment the nurse by mistake, instead of furosemide, intravenously administered her pancuronium. Sudden respiratory and circulatory arrest occurred, so she was intubated and resuscitation with artificial ventilation were undertaken, however within 1 hour and 45 minutes the patient died. Due to the vague background of a sudden deterioration in the patient's condition, the case was brought for prosecution. The autopsy and histopathological studies did not reveal the cause of death, but undertaken chemico-toxicological examinations identified the presence of pancuronium in blood, liver and kidney (190 ng/ml, 70 ng/g and 125 ng/g, respectively). Chemico-toxicological analysis proved that the cause of death of the 57-year-old hospitalized woman was pancuronium intoxication due to evident medical error during drug administration. In our case the concentration of pancuronium in blood was in therapeutic range (200-600 ng/ml). However, even a therapeutic pancuronium dose administered to patient the breath of whom is not supported and monitored can be a threat to his life.

Pancuronium enhances isoflurane anesthesia in rats via inhibition of cerebral nicotinic acetylcholine receptors.

PURPOSE: This study was conducted to elucidate the mechanism of enhancement of volatile anesthetics by neuromuscular blocking agents in rats and to consider the relevance of this enhancement to clinical anesthesia. METHODS: Male Sprague-Dawley rats were used. After confirming a movement in response to tail clamping under 1.1 % isoflurane anesthesia, response was determined when the tail clamp was applied at several points after microinjection of pancuronium into the lateral ventricle. Arousal responses to microinjection of nicotine into the lateral ventricle were assessed with or without pretreatment with intraventricular pancuronium. The intravenous 50 % effective dose (ED50) and 95 % effective dose (ED95) for neuromuscular blockade with pancuronium administered in a cumulative fashion at 1.1 % isoflurane were calculated. RESULTS: Intraventricular pancuronium dose-dependently reduced the response to tail clamping, and the dose required to show immobilization of 50 % of rats (intraventricular ED50) was 1.62 µg/kg. Pretreatment with pancuronium at 6 µg/kg significantly reduced the effect of awakening by nicotine under isoflurane anesthesia (P = 0.044). The intravenous ED50 and ED95 for neuromuscular blockade were 63 µg/kg (90 % confidence interval [CI] 52-75 µg/kg) and 133 µg/kg (90 % CI 109-158 µg/kg), respectively. The ratio of intraventricular ED50 to intravenous ED50 was 0.026. CONCLUSION: Pancuronium microinjection into the lateral ventricle dose-dependently enhances the depth of isoflurane anesthesia, which might be caused by inhibition of neuronal nicotinic acetylcholine receptor transmission in the cerebrum. Intravenous injection of pancuronium at high doses might increase the cerebrospinal concentration to a level at which an effect can be observed.

Interrupted (self -)medication with pancuronium(bromide) and fatal outcome.

Pancuronium(bromide) is used because of its relaxing effect on striated muscles and usually requires artificial respiration. A 52-year-old woman suffered from long-standing "generalized dystonia", which had become resistant to conventional therapy. Therefore, an anesthetist established a permanent medication scheme with pancuronium using a PCA pump. This pump had been controlled by the patient herself ensuring an acceptable quality of life with broad personal autonomy. Finally, the woman was found dead in her flat by a member of a home nursing service. The infusion hose showed a fixed knot and further blocking by a clamp. The autopsy findings were non-specific, except for the presence of opioid tablets in the colon. Toxicological analyses showed 72ng/ml pancuronium and 21 ng/ml oxycodone (therapeutic) in the femoral venous blood. The range of published pancuronium levels varies from approx. 80 to 2,000 ng/ml. Thus it had to be assumed that the pancuronium level was too low (72 ng/ml) so that symptoms of dystonia recurred. Based on extensive literature research, the described case can be qualified as unique. The therapy concept had been innovative, sufficient and effective for more than 10 years. It allowed the patient to enjoy a maximum of autonomy. Ultimately, death was due to the blocked pancuronium infusion. The relatively low pancuronium level had provoked the dystonia to return with generalized spasms also involving the respiratory muscles resulting in respiratory arrest. During the police investigations, two previous suicide attempts came to light.

Comparative pharmacodynamics of pancuronium, cisatracurium, and CW002 in rabbits.

Pancuronium is a long-duration neuromuscular blocking drug (NMBD) that has been used in anesthetized rabbits at 0.1 mg/kg. However, there are limited data regarding the time course for recovery from this dose either spontaneously or with pharmacologic reversal. Here we defined the potency, onset, and recovery characteristics for the intermediate-duration NMBD cisatracurium and CW002 (a novel cysteine-inactivated molecule) in the rabbit, and test the hypothesis that these drugs may be alternatives to 0.1 mg/kg pancuronium for survival procedures. New Zealand white rabbits anesthetized with isoflurane were studied in a cross-over design. Potencies of cisatracurium and CW002 were defined as the effective dose for 95% depression of evoked muscle twitch (ED95). Responses to 3×ED95 were used to define onset (time to maximal effect), recovery index (RI; time from 25% to 75% recovery of twitch), and duration (time to complete recovery). Responses to all drugs were determined with and without reversal by neostigmine-glycopyrrolate or L-cysteine. CW002 was 4-fold more potent than was cisatracurium, but their onset, RI, and duration were similar. Pancuronium had similar onset and RI but longer duration, compared with cisatracurium and CW002. Reversal shortened the recovery index and duration for all 3 drugs. At 3×ED95, cisatracurium and CW002 had the same onset as did standard-dose pancuronium, but durations were shorter and more predictable. In addition, CW002 can be reversed without the potential side effects of cholinergic manipulation. We conclude that cisatracurium and CW002 are viable alternatives to pancuronium for survival studies in rabbits.

Medication errors in anaesthetic practice: a report of two cases and review of the literature.

BACKGROUND: Mistakes in the identification and administration of drugs may be fatal. This is especially so in the practice of anaesthesia. This is a report of 2 cases of near fatality due to mistakes in drug administration from look-alike medications. OBJECTIVE: To highlight the significance of medication errors in our practice and to discuss the best methods of prevention. METHOD: A report of two cases of errors in the administration of drugs during the conduct of anaesthesia. The subsequent management of the cases is presented, and the findings from the literature are discussed. RESULT: In case 1, an adult male presented for herniorrhaphy and after induction with propofol 1mg/kg intravenously, Pancuronium bromide injection 4 mg was administered intravenously, in the place of suxamethonium chloride injection. In case 2, For induction of anaesthesia, 100mg of thiopentone sodium was administered in place of 25mg of the same drug because Thiopentone 1 gm vial was mistaken for Thiopentone 500 mg vial in a 2 year old girl. In both cases, the errors were detected early and there were no adverse sequelae. CONCLUSION: Medication errors are a potential source of iatrogenic harm to patients undergoing anaesthesia. Strict adherence to principles as well as constant vigilance would minimize this problem.

Neuromuscular blockade and lung function during resuscitation of infants with congenital diaphragmatic hernia.

BACKGROUND: There is no consensus or evidence as to whether a neuromuscular blocking agent should be used during the initial resuscitation of infants with congenital diaphragmatic hernia (CDH) in the labour ward. OBJECTIVE: To determine if administration of a neuromuscular blocking agent affected the lung function of infants with CDH during their initial resuscitation in the labour ward. METHODS: Fifteen infants with CDH were studied (median gestational age 38 weeks, range 34-41; birth weight 2,790 g, range 1,780-3,976). Six infants had undergone feto-endotracheal occlusion (FETO). Flow, airway pressure, tidal volume and dynamic lung compliance changes were recorded using a respiratory function monitor (NM3, Respironics). Twenty inflations immediately before, immediately after and 5 min after administration of a neuromuscular blocking agent (pancuronium bromide) were analysed. RESULTS: The median dynamic lung compliance of the 15 infants was 0.22 ml/cm H2O/kg (range 0.1-0.4) before and 0.16 ml/cm H2O/kg (range 0.1-0.3) immediately after pancuronium bromide administration (p < 0.001) and remained at a similar low level 5 min after pancuronium bromide administration. The FETO compared to the non-FETO infants had a lower median dynamic compliance both before (p < 0.0001) and 5 min after pancuronium administration (p < 0.001) and required significantly longer durations of ventilation (p = 0.004), supplementary oxygen (p = 0.003) and hospitalisation (p = 0.007). CONCLUSIONS: Infants with CDH, particularly those who have undergone FETO, have a low lung compliance at birth, and this is further reduced by administration of a neuromuscular blocking agent.

Pancuronium dose refinement in experimental pigs used in cardiovascular research.

OBJECTIVE: To quantify the dose of pancuronium required to obtain moderate neuromuscular blockade as monitored by acceleromyography (NMB(mod) : train-of-four count of ≤2) as a part of a balanced anaesthetic protocol in pigs used in cardiovascular research. STUDY DESIGN: Prospective cross-sectional study. ANIMALS: Five pigs (median body weight: 60 (range 60-63) kg). METHODS: Anaesthesia was induced with xylazine, ketamine, atropine and midazolam and maintained with isoflurane in O(2) :air and fentanyl. Pigs received 0.1 mg kg(-1) pancuronium initial bolus to reach NMB(mod) followed by 0.1 mg kg(-1) hour(-1) constant rate infusion (CRI). During anaesthesia a twitch count of 3 or measureable T4/T1 ratio indicated unsatisfactory NMB. In this case additional 0.4 mg boluses of pancuronium were administered IV to effect in addition to the CRI. Descriptive statistical analysis was performed to express the median and range of the bolus and CRI dose of pancuronium in pigs. Cardiovascular parameters were analyzed at selected time points with Friedman Repeated Measures Analysis on Ranks. Spearman Rank test was used to evaluate correlation between parameters. RESULTS: Acceleromyographic monitoring of NMB is feasible in anaesthetized pigs. The median initial dose and rate of pancuronium required to achieve NMB(mod) were 0.10 (range 0.10-0.13) mg kg(-1) and 0.11 (range 0.10-0.21) mg kg(-1) hour(-1) , respectively. The administration rate showed considerable individual variation. CONCLUSIONS AND CLINICAL RELEVANCE: These pancuronium doses can be used as a guideline to achieve NMB(mod) in pigs as part of a balanced anaesthetic protocol. Instrumental NMB monitoring is essential because of individual kinetic variations and compliance to monitoring guidelines.

Altered vascular endothelial growth factor expression during GnRH antagonist protocol in women of reproductive age with normal baseline hormone profiles.

OBJECTIVE: To explain the unexpected low response to GnRH antagonist protocol in reproductive women with normal baseline hormone profiles. DESIGN: Retrospective study. SETTING: University hospital. PATIENT(S): Twenty-five women undergoing their first IVF cycle. INTERVENTION(S): Follicular fluid (FF) from large follicles (>15 mm) was obtained during oocyte retrieval from unexpected low responders (n = 13, group A) and 12 age-matched normal responders (n = 12, group B). MAIN OUTCOME MEASURE(S): The FF markers known to reflect follicle environment (insulin-like growth factor [IGF] II, IGF-binding protein 4, müllerian-inhibiting substance, pregnancy-associated plasma protein A, soluble Fas, and vascular endothelial growth factor [VEGF]) were analyzed by ELISA. RESULT(S): The baseline characteristics (age, day 3 serum LH, FSH, E(2), duration and dose of r-FSH, GnRH antagonist) were not different between the two groups. The number of large follicles, oocytes retrieved, and serum E(2) levels on the day of hCG injection were significantly higher in group B. Whereas the other follicular markers did not differ between the two groups, VEGF was significantly higher in group A. In addition, the VEGF concentration showed an inverse correlation with the total number of oocytes retrieved. CONCLUSION(S): The unexpected low response in women with normal basal hormone profiles, during GnRH antagonist protocol, was associated with altered follicular VEGF expression.

The medical-legal quandary of healthcare in capital punishment: an ethical dilemma for the anesthesia provider.

The case of Brase v Rees was presented before the US Supreme Court to consider the constitutionality of death by lethal injection as practiced in the state of Kentucky. The 3-drug combination of sodium thiopental, pancuronium bromide, and potassium chloride is a key aspect in question. Capital punishment conflicts with medical and nursing code of ethics preventing providers who are skilled at difficult intravenous (IV) access, assessment of appropriate sedation, and involvement without fear of disciplinary action. Therefore, untrained or undertrained personnel from the prison have been delegated these duties. Cases in which failure to establish or maintain IV access has led to executions lasting up to 90 minutes before the execution was complete. Participation by skilled medical personnel has been a debate between the medical and legal communities since the inception of lethal injection. Healthcare should reevaluate the ethical and moral principle of beneficence as the legal system attempts to evaluate the constitutionality of lethal injection. Can a nurse or doctor step out of the role of medical professional, use knowledge and skill to make death by lethal injection more humane, and not violate the ethical principle of "do no harm"?

Issues surrounding lethal injection as a means of capital punishment.

Lethal injection as a method of state-sanctioned capital punishment was initially proposed in the United States in 1977 and used for the first time in 1982. Most lethal injection protocols use a sequential drug combination of sodium thiopental, pancuronium bromide, and potassium chloride. Lethal injection was originally introduced as a more humane form of execution compared with existing mechanical methods such as electrocution, toxic gassing, hanging, or firing squad. Lethal injection has not, however, been without controversy. Several states are considering whether lethal injection meets constitutional scrutiny forbidding cruel and unusual punishment. Recently in the case of Ralph Baze and Thomas C. Bowling, Petitioners, v John D. Rees, Commissioner, Kentucky Department of Corrections et al, the United States Supreme Court upheld the constitutionality of the lethal injection protocol as carried out in the Commonwealth of Kentucky. Most of the debate has surrounded the dosing and procedures used in lethal injection and whether the drug combinations and measures for administering the drugs truly produce a timely, pain-free, and fail-safe death. Many have also raised issues regarding the "medicalization" of execution and the ethics of health care professionals' participation in any part of the lethal injection process. As a result of all these issues, the future of lethal injection as a means of execution in the United States is under significant scrutiny. Outcomes of ongoing legislative and judicial reviews might result in cessation of lethal injection in totality or in alterations involving specific drug combinations or administration procedures.

Improved neuromuscular blockade using a novel neuromuscular blockade advisory system: a randomized, controlled, clinical trial.

BACKGROUND: Conventional incremental bolus administration of neuromuscular blocking (NMB) drugs is associated with limitations in intraoperative control, potential delays in recovery, and residual blockade in the postanesthetic period. To overcome such limitations, we developed a novel adaptive control computer program, the Neuromuscular Blockade Advisory System (NMBAS). The NMBAS advises the anesthesiologist on the timing and dose of NMB drugs based on a sixth-order Laguerre model and the history of the patient's electromyographic responses. Here, we tested the hypothesis that the use of the NMBAS improves NMB compared to standard care. METHODS: We conducted a prospective, randomized, controlled, blinded, parallel-group, clinical trial with n = 73 patients (ASA physical status I-III) undergoing abdominal surgery under general anesthesia > or =1.5 h with NMB using rocuronium. Patients were allocated to standard care or NMBAS-guided rocuronium administration. The primary outcome variable was the incidence of intraoperative events reflecting inadequate NMB. Secondary outcome variables included train-of-four (TOF) ratios at the end of surgery before reversal, the total doses of rocuronium, reversal agents, anesthetics and other drugs, the incidence of postoperative adverse events, and the incidence of anesthesiologist noncompliance with NMBAS recommendations. RESULTS: Of 73 enrolled patients, n = 30 per group were eligible for analysis. Patient demographics were comparable between the groups. The incidence in total intraoperative events associated with inadequate NMB was significantly lower in the NMBAS group compared to standard care (8/30 vs 19/30; P = 0.004). Mean TOF ratios at the end of surgery before reversal were higher in the NMBAS group (0.59 [95% CI, 0.48-0.69] vs 0.14 [95% CI, 0.04-0.24]; P < 0.0001). Total administered doses of rocuronium, reversal drugs, and other drugs, and the incidence of postoperative adverse events were not different. CONCLUSIONS: Compared to standard practice, NMBAS-guided care was associated with improved NMB quality and higher TOF ratios at the end of surgery, potentially reducing the risk of residual NMB and improving perioperative patient safety.

Neuromuscular blockade in cardiac surgery: an update for clinicians.

There have been great advancements in cardiac surgery over the last two decades; the widespread use of off-pump aortocoronary bypass surgery, minimally invasive cardiac surgery, and robotic surgery have also changed the face of cardiac anaesthesia. The concept of "Fast-track anaesthesia" demands the use of nondepolarising neuromuscular blocking drugs with short duration of action, combining the ability to provide (if necessary) sufficiently profound neuromuscular blockade during surgery and immediate re-establishment of normal neuromuscular transmission at the end of surgery. Postoperative residual muscle paralysis is one of the major hurdles for immediate or early extubation after cardiac surgery. Nondepolarising neuromuscular blocking drugs for cardiac surgery should therefore be easy to titrate, of rapid onset and short duration of action with a pathway of elimination independent from hepatic or renal dysfunction, and should equally not affect haemodynamic stability. The difference between repetitive bolus application and continuous infusion is outlined in this review, with the pharmacodynamic and pharmacokinetic characteristics of vecuronium, pancuronium, rocuronium, and cisatracurium. Kinemyography and acceleromyography are the most important currently used neuromuscular monitoring methods. Whereas monitoring at the adductor pollicis muscle is appropriate at the end of surgery, monitoring of the corrugator supercilii muscle better reflects neuromuscular blockade at more central, profound muscles, such as the diaphragm, larynx, or thoraco-abdominal muscles. In conclusion, cisatracurium or rocuronium is recommended for neuromuscular blockade in modern cardiac surgery.

Serum antimüllerian hormone levels remain stable throughout the menstrual cycle and after oral or vaginal administration of synthetic sex steroids.

OBJECTIVE: To investigate whether oral or vaginal administration of contraceptive hormones might affect antimüllerian hormone (AMH) levels. DESIGN: Prospective trial with women recruited by advertisement. Women who wished contraception were randomized between oral or vaginal estroprogestative contraception, and those who did not choose contraception were included in the control group. SETTING: Fertility clinic of a tertiary university hospital. PATIENT(S): Twenty-four young, healthy volunteer women with regular cycles who had received no hormonal contraception for at least 3 months before the study. INTERVENTION(S): Oral or vaginal estroprogestative contraception from day 5 to 25 of a menstrual cycle versus no contraception. MAIN OUTCOME MEASURE(S): Intercycle and intracycle variations of serum AMH levels in normally ovulating volunteers and following the initiation of oral or vaginal estroprogestative contraception. RESULT(S): Fluctuations of AMH levels observed during the menstrual cycle remained within cycle-to-cycle variability in cycling controls and in women receiving oral or vaginal contraception. CONCLUSION(S): Our findings confirm that AMH levels remain steady during the menstrual cycle and indicate that they are unaffected by exogenous sex steroids used for contraception whether administered orally or vaginally.

Skin reactions to intradermal neuromuscular blocking agent injections: a randomized multicenter trial in healthy volunteers.

BACKGROUND: Numerous reports confirm the performance of intradermal tests for the diagnosis of anaphylaxis during anesthesia; however, there is controversy over their diagnostic value regarding the newer neuromuscular blocking agents (NMBAs). METHODS: One hundred eleven healthy volunteers were randomly assigned to receive intradermal injections of two NMBAs, at five increasing concentrations. A concentration was considered as a reactive concentration when it led to a positive reaction in more than 5% of the subjects. These concentrations were compared with the maximal concentration recommended for the diagnosis of sensitization to NMBAs. RESULTS: The maximal nonreactive concentrations were 10 m for suxamethonium; 10 m for pancuronium, vecuronium, rocuronium, and cisatracurium; and 10 m for atracurium and mivacurium. Except for mivacurium, these nonreactive concentrations were close to the maximal concentrations used for the diagnosis of sensitization against NMBAs. For mivacurium, the nonreactive concentrations were higher than the maximal concentration currently recommended in clinical practice. CONCLUSION: The aminosteroidal NMBAs pancuronium, vecuronium, and rocuronium and the benzylisoquinoline cisatracurium have a similar potency to induce a nonspecific skin reactivity. If the criteria for positivity and the maximal concentrations of the commercially available compounds recommended by French practice guidelines are used, the risk of false-positive results is limited, and only minor modifications of these recommendations could be suggested. A slight reduction in the maximal concentration used for rocuronium from 1:100 to 1:200 and an increase from 1:1,000 to 1:200 for mivacurium can be proposed.