Diphenhydramine for Acute Extrapyramidal Symptoms After Propofol Administration James Sherer, BA, Tomas Salazar, BE, Kevin B

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Diphenhydramine for Acute Extrapyramidal Symptoms After Propofol Administration James Sherer, BA, Tomas Salazar, BE, Kevin B. Schesing, BA, Shannon McPartland, BS, Jeffrey Kornitzer, MD

Extrapyramidal symptoms are an uncommon but well-recognized side abstract effect after the administration of general anesthesia in patients without a significant neurologic history. Several case reports implicate propofol as the likely causative agent producing these symptoms, which include ballismus, dystonia, choreoathetosis, and opisthotonus. Currently, there is no clear consensus on first-line treatment of these symptoms. In each of the published cases, anticholinergic medications and benzodiazepines Department of Neurology, Rutgers New Jersey Medical were central to initial management, although the speed and extent of School, Newark, New Jersey symptom resolution were variable. Here we present a case of a 17-year- Mr Sherer performed the literature review, drafted old boy with ulcerative colitis who presented with ballismus, torticollis, the original case report, edited the fi nalized case tongue thrusting, and oculogyric movements after colonoscopy under report, and coordinated with co-authors; Mr Salazar reviewed the details of the case and aided general anesthesia with propofol. The patient responded promptly to in drafting the original case report; Mr Schesing treatment with diphenhydramine. This is the first reported case in which reviewed the literature and aided in drafting the diphenhydramine was successfully used as the primary treatment of original case report; Ms McPartland reviewed the severe extrapyramidal symptoms in a pediatric patient after propofol literature, aided in drafting the original case report, and edited the fi nalized case report; Dr Kornitzer administration. diagnosed and treated the patient discussed in the case report, conceptualized the original case report, and edited and critically reviewed the case report; and all authors approved the fi nal An intravenous anesthetic agent been effective in only a minority of manuscript as submitted. cases.4 Our case demonstrates how a commonly used in the pediatric DOI: 10.1542/peds.2016-1135 population, propofol is approved by regimen of diphenhydramine followed Accepted for publication Oct 10, 2016 the US Food and Drug Administration by benztropine may be an effective for anesthesia maintenance in patients treatment for relief of extrapyramidal Address correspondence to Jeffrey Kornitzer, MD, Department of Neurology, Rutgers New Jersey symptoms caused by propofol. >2 months old and for anesthesia Medical School, Suite 5300, 90 Bergen Street, induction in patients >3 years old. 1 Newark, NJ 07103. E-mail: [email protected] With wide clinical use, propofol PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, is considered invaluable by many CASE 1098-4275). physicians, given its overall safety A 17-year-old boy with ulcerative Copyright © 2017 by the American Academy of 2 and efficacy in patients of all ages. colitis presented with severe Pediatrics However, propofol may cause a extrapyramidal symptoms after FINANCIAL DISCLOSURE: The authors have number of well-recognized adverse a colonoscopy under general indicated they have no fi nancial relationships relevant to this article to disclose. reactions, including hypotension, anesthesia. At home, the patient took injection site burning, apnea, and mercaptopurine 75 mg and 100 mg FUNDING: No external funding. central nervous system (CNS) effects. 3 on alternating days, mesalamine POTENTIAL CONFLICT OF INTEREST: The authors The CNS effects of propofol are varied 2.4 mg daily, omeprazole 20 mg twice have indicated they have no potential confl icts of interest to disclose. and well documented, ranging from daily, and a multivitamin daily. The prolonged unresponsiveness to patient had never experienced an abnormal movements. 3 Treatment of adverse reaction to any medication, To cite: Sherer J, Salazar T, Schesing KB, et al. the CNS side effects of propofol has and there was no family history of Diphenhydramine for Acute Extrapyramidal traditionally consisted of a cocktail anesthesia problems. The procedure Symptoms After Propofol Administration. Pediatrics. 2017;139(2):e20161135 of benzodiazepines, although it has was performed with propofol 200 mg,

Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 139 , number 2 , February 2017 :e 20161135 CASE REPORT lidocaine 60 mg, and sevoflurane not recur, the patient was maintained literature review describes the use 2%. To reduce the risk of aspiration on intravenous diphenhydramine of benzodiazepines as treatment during the procedure, given for the next 2 days, with the dosage in 7 reported cases. 4 In 5 of these vomiting and gastroesophageal tapered from 25 mg every 6 hours cases, there was no response to reflux in the days leading up to the the first day to 12.5 mg every 6 hours treatment, and the remaining 2 cases colonoscopy, the anesthesiologist the second day. He had no more displayed only partial remission of used rapid induction with abnormal movements. symptoms. The only documented succinylcholine 100 mg, followed patient to achieve complete by uncomplicated intubation. remission of extrapyramidal The patient did not receive DISCUSSION symptoms was treated with ondansetron, metoclopramide, or biperiden, an anticholinergic In addition to propofol, many any other antiemetic medication, agent. 4 Interestingly, none of the anesthetics, including sevoflurane, because he did not complain of published cases report treatment thiopentone, and etomidate, have nausea or vomiting the morning with diphenhydramine, despite been associated with extrapyramidal of the colonoscopy. The procedure the fact that diphenhydramine movements. Propofol is of particular lasted for 1 hour. Shortly after is often used as prophylaxis for interest because of its widespread regaining consciousness, the patient extrapyramidal symptoms caused use for anesthesia induction and experienced violent, uncontrolled by other medications, such as maintenance in the pediatric bilateral ballismus involving all 4 metoclopramide. 15 population. Although there are a extremities. Additionally, he had number of reports of abnormal Our treatment regimen builds on torticollis, intermittent tongue movements associated with the successful treatment with an thrusting, and sporadic oculogyric propofol, 5 – 11 no clear treatment has anticholinergic described in the crises. Despite the movements, he been developed. Reported reactions literature but uses diphenhydramine remained awake and communicative to propofol include opisthotonus, rather than biperiden for its throughout these events, stating that a state of spine and extremity anticholinergic properties. he was unable to control his arms, hyperextension. 5 Dystonic reactions, Previously, diphenhydramine has legs, neck, and eyes. During this time such as intermittent or sustained been used to aid in the treatment the patient’s cardiopulmonary status contractions of muscles in the face, of movement disorders in the remained stable, he had no tongue larynx, trunk, pelvis, and extremities, pediatric population, 16 – 18 but it biting, and he did not exhibit bladder have also been detailed in the has not specifically been used to or bowel incontinence. literature. 6– 8 Our patient experienced treat extrapyramidal symptoms oculogyric crisis (with prolonged associated with propofol use. Midazolam 2 mg was administered upward deviation of the eyes), a rare In this case, prompt and nearly intravenously without relief of side effect previously reported in complete resolution of severe symptoms, and the patient was association with propofol. 12 Although symptoms was achieved with 50 mg transferred to the postanesthesia the neuroexcitatory mechanisms of diphenhydramine alone, although full care unit. Because of continuing propofol are not well understood, 13 resolution required the addition of symptoms, he received 1 mg it is hypothesized that the potential 2 mg benztropine soon after. Benefits intravenous lorazepam and an extrapyramidal effects of propofol of using diphenhydramine in this way additional 2 mg midazolam. When result from activation of excitatory include its widespread availability the patient did not respond to these pathways in the subcortical region, and limited side effects at low medications, the neurology team was 19 extended refractory periods in dosages. Although more research consulted. After determining him to inhibitory pathways in the brainstem is clearly indicated, we suggest that be having an extrapyramidal reaction and spinal cord, or a combination of giving diphenhydramine, followed by to propofol, the neurology team both. 14 benztropine for lingering movements, gave the patient diphenhydramine and then a diphenhydramine taper 50 mg intravenously. Within several Recent therapeutic attempts aimed is an effective and safe approach to minutes, there was near complete at alleviating extrapyramidal treating extrapyramidal symptoms cessation of all extrapyramidal symptoms associated with propofol associated with propofol use. movements. Some lingering, have included anticholinergics intermittent, athetoid movements and benzodiazepines, but these were completely halted by 2 mg interventions have led to suboptimal benztropine administered 30 minutes outcomes. 4 In the literature to ABBREVIATION after diphenhydramine was given. To date, there is no clear consensus on CNS: central nervous system ensure that these symptoms would treatment of these symptoms. One

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Downloaded from www.aappublications.org/news by guest on September 26, 2021 Diphenhydramine for Acute Extrapyramidal Symptoms After Propofol Administration James Sherer, Tomas Salazar, Kevin B. Schesing, Shannon McPartland and Jeffrey Kornitzer Pediatrics 2017;139; DOI: 10.1542/peds.2016-1135 originally published online January 5, 2017;

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