Response to “Remifentanil‐Induced Chest Wall Rigidity in an Infant With Hepatic Failure”

Fentanyl-Induced Chest Wall Rigidity

BackgroundChest wall rigidity is a known side effect of fentanyl use, which is why fentanyl is usually combined with a muscle relaxant such as mivacurium. Verifying endotracheal intubation is difficult in case of a rigid chest wall.Case presentationWe present the case of a preterm infant (29 completed weeks gestation, birth weight 1,150 g) with a prolonged chest wall rigidity after fentanyl administration for intubation despite adequate doses of mivacurium. This resulted in a pronounced desaturation without any effect on heart rate. Clinically, the infant showed no chest wall movement despite intubation and common tools to verify intubation (including end-tidal carbon dioxide measurement and auscultation) were inconclusive. However, using electrical impedance tomography (EIT), we were able to demonstrate minimal tidal volumes at lung level and thereby, EIT was able to accurately show correct placement of the endotracheal tube.ConclusionsThis case may increase vigilance for fentanyl-induced chest wall rigidity in the neonatal population even when simultaneously administering mivacurium. Higher airway pressures exceeding 30 mmHg and the use of μ-receptor antagonists such as naloxone should be considered to reverse opioid-induced chest wall rigidity. Most importantly, our data may imply a relevant clinical benefit of using EIT during neonatal intubation as it may accurately show correct endotracheal tube placement.

IntroductionOpiate-induced chest wall rigidity is a syndrome that largely goes unrecognized. To date, no study has presented significant objective data to better understand this syndrome.ObjectiveThe aim of this study was to explore the correlation between the dosage of opiates and the incidence of chest wall rigidity, ventilatory changes, and effects of naloxone administration.MethodsA total of eight patients were identified as having episodes of chest wall rigidity, with half of the population being females, with an average age of 54.8 ± 9 years. Physiological changes, ventilator data, vitals, and opiate dosage prior to chest wall rigidity episodes and after reversal with naloxone administration were analyzed using the Wilcoxon rank sum test for statistical significance.ResultsSignificant changes were observed in dynamic wall compliance without positive end-expiratory pressure (PEEP) (pre-median=5.13; post-median=52.03; p=0.0078), dynamic wall compliance with PEEP (pre-median=6.13; post-median=72.36; p=0.0078), tidal volume (pre-median=110.5; post-median=1006; p=0.0078), and ventilator airflow (pre-median=0; post-median=75; p=0.0078). However, no statistically significant changes were detected in end tidal CO2 (pre-median=36; post-median=37.5; p=0.4219), respiratory rate (pre-median=9; post-median=10.5; p=0.7188), or peak airway pressure (pre-median=17; post-median=21.5; p=0.4063). Additionally, there is a statistically significant correlation between morphine equivalent potency dosing within 24 hours and the change in tidal volume (r=0.8237; p=0.0439).ConclusionsOur study is the first to demonstrate significant objective data on the ventilatory responses seen with opiate-induced chest wall rigidity. These findings may assist clinicians in better understanding the presentation and management of chest wall rigidity.

Background: There has been a significant spike in fentanyl-related deaths from illicit fentanyl supplied via the heroin trade. Past fentanyl access was primarily oral or dermal via prescription fentanyl patch diversion. One factor potentially driving this increase in fatalities is the change in route of administration. Rapid intravenous (IV) fentanyl can produce chest wall rigidity. We evaluated post-mortem fentanyl and norfentanyl concentrations in a recent surge of lethal fentanyl intoxications. Methods: Fentanyl related deaths from the Franklin County coroner’s office from January to September 2015 were identified. Presumptive positive fentanyl results were confirmed by quantitative analysis using liquid chromatography tandem mass spectrometry (LC/MS/MS) and were able to quantify fentanyl, norfentanyl, alfentanyl, and sufentanyl. Results: 48 fentanyl deaths were identified. Mean fentanyl concentrations were 12.5 ng/ml, (range 0.5 ng/ml to >40 ng/ml). Mean norfentanyl concentrations were 1.9 ng/ml (range none detected to 8.3 ng/ml). No appreciable concentrations of norfentanyl could be detected in 20 of 48 cases (42%) and were less than 1 ng/ml in 25 cases (52%). Elevated fentanyl concentrations did not correlate with rises in norfentanyl levels. In several cases fentanyl concentrations were strikingly high (22 ng/ml and 20 ng/ml) with no norfentanyl detected. Discussion: The lack of any measurable norfentanyl in half of our cases suggests a very rapid death, consistent with acute chest rigidity. An alternate explanation could be a dose-related rapid onset of respiratory arrest. Deaths occurred with low levels of fentanyl in the therapeutic range (1–2 ng/ml) in apparent non-naïve opiate abusers. Acute chest wall rigidity is a well-recognized complication in the medical community but unknown within the drug abuse community. The average abuser of illicit opioids may be unaware of the increasing fentanyl content of their illicit opioid purchase. Conclusion: In summary we believe sudden onset chest wall rigidity may be a significant and previously unreported factor leading to an increased mortality, from illicit IV fentanyl use. Fentanyl and norfentanyl ratios and concentrations suggest a more rapid onset of death given the finding of fentanyl without norfentanyl in many of the fatalities. Chest wall rigidity may help explain the cause of death in these instances, in contrast to the typical opioid-related overdose deaths. Intravenous heroin users should be educated regarding this potentially fatal complication given the increasingly common substitution and combination with heroin of fentanyl.

BackgroundResearch on remifentanil-induced chest wall rigidity is limited. Furthermore, its incidence is unknown, and the clinical factors influencing its development remain unclear. This prospective, double-blind, randomized controlled trial aimed to investigate the effects of the administration sequence of hypnotics and remifentanil as well as the type of hypnotic administered on the development of remifentanil-induced chest wall rigidity.MethodsA total of 125 older patients aged ge 65 years, who were scheduled to undergo elective surgery under general anesthesia, were enrolled in this study. Participants were randomly assigned to one of four groups; Thio-Remi, Pro-Remi, Remi-Thio, or Remi-Pro. After confirming the loss of consciousness and achieving a target effect-site concentration of 3 ng/mL remifentanil, the development of remifentanil-induced chest wall rigidity was evaluated.ResultsThe incidence of chest wall rigidity was significantly higher in the remifentanil-hypnotic group than in the hypnotic-remifentanil (opposite sequence) group (55.0% vs. 21.7%, P < 0.001). Logistic regression analysis revealed that remifentanil-hypnotic administration was a significant predictor of the development of chest wall rigidity (crude odds ratio 4.42, 95% confidence interval 1.99; 9.81, P < 0.001).ConclusionsPretreatment with hypnotics potentially reduces the development of chest wall rigidity during the induction of balanced anesthesia with remifentanil in older patients.Trial registrationThis article was registered at WHO International Clinical Trials Registry Platform (Trial number: KCT0006542).

Intravenous bolus (IVb) injection of fentanyl induces an immediate apnea, but the characteristics of the apnea and relevant mechanism remain unclear. Here, we tested whether IVb injection of fentanyl induced an immediate central and upper airway obstructive apnea associated with chest wall rigidity via activating vagal C-fibers (VCFs) and vagal afferent opioid receptors (ORs). Cardiorespiratory and electromyography of external and internal intercostal, thyroarytenoid, and superior pharyngeal constrictor muscles (EMGEI, EMGII, EMGTA, and EMGSPC) responses to IVb injection of fentanyl were recorded in anesthetized and spontaneously breathing rats with or without bilateral perivagal capsaicin treatment or intravagal microinjection of naloxone. An immunohistochemical approach was employed to define the presence of opioid mu-receptor (MOR) expression in vagal C-neurons, and a patch clamp technique was utilized to determine the evoked current responses of vagal C-neurons to fentanyl in vitro. Fentanyl induced an immediate apnea and subsequent respiratory depression. The apnea was characterized by cessation of EMGEI activity and augmentation of tonic discharges of EMGII, EMGTA, and EMGSPC, i.e., central expiratory apnea, laryngeal closure, and pharyngeal constriction/collapse accompanied with chest wall rigidity. The apneic response was abolished by blockade of VCF signal conduction and largely attenuated by antagonism of vagal afferent ORs. The latter significantly alleviated the initial (within 5-min postinjection), but not the latter, respiratory depression. Vagal C-neurons expressed MORs and were activated by fentanyl. We conclude that IVb injection of fentanyl causes a VCF- and vagal afferent OR-mediated immediate central apnea, upper airway obstruction, and chest wall rigidity.NEW & NOTEWORTHY Intravenous bolus injection of fentanyl triggers an immediate apnea, but the nature of apnea and relevant mechanisms remain unknown. Results in this study reveal that this fentanyl injection concurrently triggers an immediate central and upper airway obstructive apnea associated with chest wall rigidity via activating vagal sensory C-fibers.

BackgroundThe process of prescribing and preparing premedication for intubation needs to be completed carefully to ensure the correct dose is prescribed and administered. Doses of atropine, suxamethonium and fentanyl were...

Background: Wooden chest syndrome (WCS) is a known manifestation of fentanyl toxicity, especially with high doses used for anesthetic induction in rapid sequence intubation (RSI). We present a rare case of WCS leading to cardiopulmonary arrest (CPA) following administration of low dose fentanyl. Case Report: A 37-year-old woman with no past medical history was admitted for management of septic abortion complicated by respiratory failure requiring mechanical ventilation. With clinical improvement, a spontaneous breathing trial (SBT) was attempted. Given respiratory acidosis during SBT, mechanical ventilation was continued. 25 micrograms (mcg) IV fentanyl bolus was given for analgesia. A few minutes later, she developed abdominal and chest wall rigidity with agonal breathing, culminating in CPA. Telemetry rhythm strip revealed asystole. Cardiopulmonary resuscitation (CPR) was initiated. She had absent breath sounds and high airway resistance causing difficulty with bag-mask ventilation. Arterial blood gas revealed hypoxia and hypercapnia. She achieved return of spontaneous circulation within a few minutes of CPR. CXR ruled out pneumothorax. She received 25mcg IV fentanyl bolus for sedation while undergoing CT chest and had another episode of chest wall rigidity. Cisatracurium was started. Her chest wall rigidity resolved and she was extubated the next day. Discussion: Our patient likely had WCS from fentanyl toxicity demonstrated by recurrence of chest wall rigidity with fentanyl doses. WCS should be suspected in patients who develop chest wall rigidity following fentanyl administration. It should be managed with ventilator support and reversal with naloxone or a short acting neuromuscular blocker. Conclusion: CPA is a rare but fatal complication of WCS. WCS can occur with low doses of fentanyl even in patients who have previously tolerated higher doses.

Remifentanil‐Induced Chest Wall Rigidity in an Infant With Hepatic Failure

Fentanyl is in many neonatal intensive care units the sedative of choice. One side-effect is, however, the possibility of muscle and/or chest wall rigidity. A pregnant woman with a critical pulmonary valve stenosis had a balloon dilatation at 26 weeks of gestation. She was put on propranolol, but went into a severe cardiac failure. In week 31, she developed pregnancy induced hypertension. Periodically absent diastolic flow in the umbilical cord was demonstrated. A Caesarean section was performed using fentanyl as analgesia. A boy weighing 1440 g, had a 1 min Apgar score of 3 without respiratory movements. Mask ventilation was tried, but chest wall expansion was not achieved despite using high pressures. He was intubated and positive pressure ventilation attempted, with the same result. Despite the use of high pressures up to 60-70 cm H2O, no chest movement could be achieved. An intravenous line was established in order to give naloxone and pancuronium. Just before the drugs were given, chest wall movements were achieved and the heart rate normalized. This is the first report on chest wall rigidity in a neonate after administration of fentanyl to the mother during Caesarean section.

Rabbit model of chest wall rigidity induced by fentanyl and the effects of apomorphine

Since its introduction into clinical practice, it has been known that fentanyl and other synthetic opioids may cause skeletal muscle rigidity. Involvement of the respiratory musculature, laryngeal structures, or the chest wall may impair ventilation, resulting in hypercarbia and hypoxemia. Although most common with the rapid administration of large doses, this rare adverse effect may occur with small doses especially in neonates and infants. We present 2 infants who developed chest wall rigidity, requiring the administration of neuromuscular blocking agents and controlled ventilation after analgesic doses of fentanyl. Previous reports regarding chest wall rigidity after the administration of low-dose fentanyl in infants and children are reviewed, the pathogenesis of the disorder is discussed, and treatment options offered.

This study compared the effectiveness of nalmefene and fentanyl in reducing the incidence and severity of etomidate-induced myoclonus. One hundred fifty patients were randomized to receive 0.25ug/kg of nalmefene, 1ug/kg of fentanyl, or the same volume of normal saline 3 minutes prior to etomidate-induced anesthesia. The primary observational indexes were the severity level and incidence of etomidate-induced myoclonus, and the secondary observational index included blood pressure, heart rate, and the incidence of adverse effects from anesthesia induction to resuscitation, such as cough, chest wall rigidity, dizziness, nausea, pain after awakening, and intraoperative awareness. The incidence of myoclonus was significantly lower in the nalmefene group (8.0%) than in the fentanyl group (32.0%) (P = .003) and in the normal saline group (72.0%) (P = .000). The severity level of myoclonus in the nalmefene group was significantly lower than the fentanyl group (P = .001) and normal saline group (P = .000). Meanwhile, the incidences of cough and chest wall rigidity during anesthesia induction were significantly lower in the nalmefene group compared with the fentanyl group (P = .003, P = .027). There were no statistically significant differences in heart rate and mean arterial pressure among the 3 gruops (P > .05). There was no difference in the incidence of adverse effects among the 3 groups during recovery from anesthesia (P > .05). Intravenous injection of 0.25ug/kg of nalmefene 3 minutes prior to etomidate is more effective in preventing etomidate-induced myoclonus during general anesthesia than 1ug/kg of fentanyl.

Chest wall rigidity during infusion of fentanyl in a two-month-old infant after heart surgery

Alfentanil, a new ultra short-acting, potent, synthetic narcotic was evaluated as an anesthetic induction agent in 20 unsedated, patients premedicated with atropine about to undergo general surgical operations with halothane-nitrous oxide anesthesia (group I) and in 22 patients premedicated with lorazepam and atropine [nine with mitral valvular disease (group II), and 13 with coronary artery disease (group III)], about to undergo open-heart surgery with alfentanil-oxygen anesthesia. Patients in groups II and III had radial and thermodilution pulmonary arterial catheters in place before anesthetic induction. Following pretreatment with pancuronium (1.5 mg/70 kg) and while breathing pure oxygen, alfentanil was administered intravenously at a rate of 50 μg/kg/min until the patient was unconscious. Cardiovascular dynamics were measured before and after pancuronium, at the point of unconsciousness, following succinylcholine paralysis, and 1 and 4 minutes after endotracheal intubation. The time of induction and the incidence of arrhythmias, chest wall rigidity, and pain on injection were also recorded. Loss of consciousness was rapid, 134 ± 28, 47 ± 19, and 75 ± 22 seconds in groups I, II, and III, respectively. Alfentanil resulted in a transient small decrease in systolic arterial blood pressure with loss of consciousness in groups II and III but no change in right atrial and mean pulmonary arterial pressures or cardiac output throughout the study period. Patients in group I had no change in any cardiovascular variable measured. The only significant undesirable side effect was chest wall rigidity, which occurred in 50% of group I and 22% and 31 % of groups II and III, respectively. No patient remembered any aspect of laryngoscopy, endotracheal intubation, or surgery and only one thought the anesthetic induction was unpleasant. These data indicate that rapid infusion with alfentanil results in a rapid, pleasant anesthetic induction with little change in cardiovascular dynamics and a minimum of side effects.