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

ELSEVIER

Chest Wall Rigidity During Infusion of Fentanyl in a Two-Month-Old Infant After Heart Surgery Drew A. MacGregor,

MD, * Loren A. Bauman,

MDT

From the Departments of Anesthesia (Critical Care), Medicine (Pulmonary/Critical Care Medicine), and Pediatrics, The Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina

Keywords: Chest wall rigidity; muscular

rigidity;

narcotics;

fentanyl; pediatrics

opioids.“-” W e d escribe a case of CWR caused by low dose fentanyl given as a continuous infusion of 4.3 pg/kg/hr without loading dose, which resulted in severe hypoventilation, acidosis, and cardiac arrest in an infant following cardiac surgery.

hypoventilation;

Introduction of Chest wall rigidity (0%~) is a common complication potent opioids given as bolus injections, most often as anesthetic induction agents. Fentanyl is a synthetic opioid agonist that is approximately 100 times more potent than morphine. When given as a small bolus injection, fentanyl 100 pg has been reported to cause CWR in an adult.’ Reports of CWR in infants are beginning to emerge as clinicians’ interests increase in providing sedation and analgesia in critically ill infants and children. Recognition that routine procedures on critically ill infants (venipunctures, endotracheal suctioning) are associated with sudden increases in blood pressure and intracranial pressure, and occasionally acute increases in pulmonary vascular resistance with profound hypoxia, has prompted the increased utilization of sedative agents and narcotics in the intensive care unit (ICU).’ Opiates such as meperidine, morphine, fentanvl, and alfentanil have been used for sedation of mechan&-ally ventilated neonates but CWR has not been reported with a low dose continuous infusion of

‘:‘AssistantPI-o&sor of Anesthesia (Gitical Oare) and Medicine (Pulmon;ll~/<:1-itical (:a~-e) t/\&rant

Professor of .-\nesthrsia (Pediatric r\nrsthesia) and Pediat-

rics (Prdiatric

(Xtical

(Iare)

Address wprint rrquests to Dr. MacGregor in the Departmrnt of Anrsthesia, Bowman Gray School of Medicine, Medical Center Blvd., Winston-S&m, NC 27157-IOOY. Receivrd for pltblication March 13, 1YY.5; revised manuscript cepted fol- publication Mav 19. lYO.5.

Journal of (:linical Anrsthesia 8251-254, 1996 0 lYY6 b) Elseviet- Science Inc. 6.55 Avrnue of the Anwricas, NW York, NY 10010

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Case Report An otherwise healthy P-month-old infant (4.6 kg) underwent surgical repair of aortic coarctation. Anesthetic induction proceeded smoothly with fentanyl 5.4 pg/kg and succinylcholine 2.1 mg/kg, followed by pancuronium 0.1 mg/kg and sequential fentanyl doses (totalling 19.5 pg/ kg) during the P-hour operation. The surgical procedure was performed without complications, and the infant returned to the ICU intubated. Over the next 36 hours in the ICU, the patient received four separate intravenous (IV) injections of morphine sulfate 0.1 mg/kg for agitation, without incident. The infant was extubated on the second postoperative day and continued to progress well. Oral formula feedings were begun on the evening following extubation. and the child was prepared to transfcl out of the ICU on the third postoperative morning. Prior to transfer, the child had increased agitation, and the nurse noted that the child appeared to aspirate a portion of the formula offered. Within the next 90 minutes, the child developed progressive respiratory difficulty, with the chest radiography eventually demonstrating a right lower lobe infiltrate, suggestive of aspiration. The child was reintubated with a 3.5 mm uncuffed endotracheal tube. The initial blood gases following intubation were satisfactory, as demonstrated in 7’&L 1. Approximately 4 hours after reintuhation the child COIItinued to he agitated, tachycardic, and restless despite normal arterial hlood gases. To provide analgesia and sedation, a fentanyl infusion was begun at 4.34 pg/kg/hr without a loading dose. Within 15 minutes, heart rate dc-

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creased from 180 to 165 beats/min, respiratory rate decreased from 56 to 38 spontaneous breaths/min, and agitation abated. The child continued to do well until 35 minutes after the initiation of the fentanyl infusion when, despite adequate pressure generation by the ventilator, the infant’s chest wall did not rise and cyanosis developed. Bag-assisted ventilation was attempted, but adequate chest expansion was not possible due to marked resistance to air flow. Fearing an obstruction, the endotracheal tube was removed, and bag-mask ventilation was attempted, but again was unsuccessful at securing ventilation. The abdominal and peripheral muscle tone was not increased and no athetoid or clonic activities were apparent. Mouth to mouth-and-nose ventilation was attempted, but again, marked resistance to air flow was noted, and the patient developed marked bradycardia and subsequent asystole. The cardiac rhythm returned with the infusion of epinephrine, but still the patient could not be adequately ventilated. Approximately 5 minutes after the return of sinus tachycardia, IV naloxone (0.5 mg; 93 pg/kg) was administered, which resulted in prompt chest wall relaxation. Ventilation was then easily accomplished, with breath sounds clearly audible in both sides of the chest. Following return of adequate oxygen saturation, the child was reintubated with a 3.5 mm endotracheal tube. Chest radiography confirmed lung expansion and no new abnormalities. At 20 minutes after reintubation, sedation and neuromuscular blockade were achieved using morphine sulfate 0.1 mg/kg and metocurine 0.1 mg/kg as bolus injections, without recurrence of CWR. The child continued to improve and was extubated 48 hours after this incident. Review with the pharmacologist confirmed that the doses and concentrations of fentanyl infusion were correct. All blood gas data are recorded in Table 1.

Discussion In one of the first descriptions of CWR due to opiates, Hamilton and Cullen’ described “a pronounced degree

Table

Tie

11:25 13:oo 14:oo 15:00* 15:15 15:40 15:50 1s:oog l&15 16:40

1.

Arterial Blood Gases and Pulse Oximetry Data

PH

7.45 7.47 7.45

7.34 7.48

PaCO, mW4)

33 32 37

44 36

PaO, @-Jw

195 222 113

375 132

0, Sat 6)

J. Clin. Anesth., vol. 8, May 1996

Vent Rate

Patient reintubated electively 99.7 30 99.8 30 98.6 27 w 27 W bag mask w mask 65-f 99.9 bag 99.1 27

*Start of fentanyl infusion. tApproximate saturation from pulse oximeter. $Pressure limit on bag-mask apparatus. SBradycardia and hypotension. PIP = peak inspiratory pressure; PEEP = positive end expiratory pressure. 252

of rigidity and increased muscle tone . . which disappeared immediately upon administration of the (opiate) antagonists.” Profound CWR with subsequent hypoventilation is a common complication of potent opioid drugs, with some reports describing it as an expected complication of anesthetic induction using opioids.s-” Other studies describe CWR as a rare occurrence.1sX14 While the true incidence of CWR following infusion of potent opioids is unclear, it appears to be dose-related.l”S1” Nevertheless, CWR has been reported with fentanyl doses as low as 100 pg given to an adult over 5 minutes in divided doses.’ CWR in neonates has been reported after bolus injections in the immediate postoperative periodI and in the neonatal intensive care unit.’ Postoperative muscle rigidity can be caused by a secondary peak effect of fentanyl, resulting from intestinal reabsorption of fentanyl sequestered in the stomach’s and increased plasma uptake from skeletal muscles enhanced by voluntary movements.“’ Intentional respiratory alkalosis may add to this trend by decreasing fentanyl clearance.‘O Bolus injections of alfentanil (a synthetic analog of fentanyl) 9 to 15 pg/kg resulted in moderate to severe CWR in 10 of 20 mechanically ventilated neonates, beginning almost immediately and lasting up to 10 minutes’; some developed rigidity with jerking and lip smacking but concurrent electroencephalographic monitoring did not suggest seizure activity. Interesting in this study was that dose and plasma levels of alfentanil did not correlate with severity of CWR.’ Nevertheless, CWR has not been previously reported using a continuous infusion of low doses of fentanyl without an initial bolus infusion. The most common opioid reported with CWR is fentanyl used in anesthetic induction, but CWR has been reported with virtually all opioids, especially the more potent drugs used in anesthesia.gX1”S16,‘1 The onset of CWR usually occurs immediately after the bolus injection, but has been reported to occur up to 24 hours after the administration of opiates.22’2” The exact mechanism of CWR from opiates has not

FiO,

0.5 0.5 0.4 0.4

1.0 1.0 1.0 1.0 0.6

PIP (cm I-W )

PEEP (cm JW)

25 25 25 25 35:: 40:: 40::

3 3 3 3

25

3

been fully defined, but central dopaminergic imbalance at the basal ganglia may be involved.‘4 Dopamine administration inhibits morphine-induced rigidity in experimental animal? although administration of amantadine hydrochloride, which releases dopamine centrally, did not block the CWR response in adults.‘” Alpha blockade with the specific ~1~adrenoreceptor blocker prazosin prevented the opiate-induced muscular rigidity noted on microin’ec24 tion of fentanyl into the brain of rats, causing Lui et al. to postulate that the noradrenergic pathway may be directly involved in the elicitation of muscular rigidity by fentanyl. In a series of experiments in rats, Negus et nl.” and Weinger et al.‘” have demonstrated attenuation of muscular rigidity due to opiates with injection of opiate antagonists into the region of periaqueductal gray matter, pontine raphe nucleus, and the nucleus reticularis tegmenti pontis. The receptors involved in muscular rigidity appear to be of the mu-l subtype, which is the same receptor that causes the antinociceptive effects of opiates.‘” Various studies have examined other drugs that may eliminate or lessen the severity of CWR. Stockham et al.‘” noted that the incidence of CWR in adults dropped to zero when fentanyl infusion of 250 pg was immediately followed by etomidate infusion. Neidhart et al.‘” showed that the severity (but not the incidence) of CWR was altered by the administration of small doses of midazolam. Ketamine does not appear to reduce the incidence of CWR, but thiopental did reduce the incidence in the same animal model.‘” Concomitant administration of a neuromuscular blocking agent (succinylcholine, pancuronium, metocurine, etc.) will prevent CWR.” A delay in giving paralytic drugs has been associated with CWR severe enough to raise central venous pressure high enough to prevent infusion of additional medicines through an IV.“‘i The treatment of CWR associated with opiates is either neuromuscular blockade (paralysis) or an opiate antagonist (~.,q., naloxone). Muscular paralysis is usually preferred, because the hemodynamic consequences of rapid reversal of opioids can be significant, including arrhythmias, hypertension, ele\ated intracranial pressure, respiratory distress, and uncontrolled pain. The most important aspect of CWR is the recognition of the process. In the case just described, CWR due to opioids was not recognized early due to the delay between starting the infusion and the onset of symptoms. The differential diagnosis in this case included tension pneumothorax (bilateral), acute airway obstruction, seizure, and other causes of extreme muscle rigidity including severe electrolyte abnormalities, none of which was present in the infant described above.

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