Akathisia preceding an oculogyric crisis in a patient treated with prochlorperazine for hyperemesis gravidarum

Introduction

Drug-induced akathisia, dystonia and neuroleptic malignant syndrome (NMS) are usually associated with high potency neuroleptics such as haloperidol and fluphenazine. Akathisia manifests itself as a strong subjective feeling of anxiety, agitation and restlessness, whereas acute dystonias can be characterised as involuntary spasms of the tongue, face, neck, back or ocular muscles, as in the case of an oculogyric crisis [1]. In extreme cases, this can lead to the development of NMS, a fatal combination of hypertonicity, autonomic dysfunction, altered mental status and hyperthermia [5]. Akathisia and focal dystonias can also occur in patients treated with low potency neuroleptics and these are known side effects to prochlorperazine [1].

We present here a case where a patient developed akathisia and an oculogyric crisis after receiving prochlorperazine for persistent nausea and vomiting.

The case

A 32-year-old female presented to the emergency room complaining of an 8-day history of vomiting and weight loss, as well as several days of spotting and suprapubic pain. She was 7 weeks into her first pregnancy, had no other past medical or psychiatric history and her only previous surgery was an appendectomy in 2006. Upon admission, she had been taking pyridoxine/doxylamine for nausea and vomiting. Initial investigations included physical exam, electrolytes, complete blood count and an ultrasound, which showed a viable intrauterine pregnancy. Urine analysis found ketones and nitrates and urine cultures found lactose positive coliforms, for which she was initially treated with nitrofurantoin. On the basis of these findings, the patient was admitted for hyperemesis gravidarum and treatment included dimenhydrinate, pantoprazole and fluid replacement. Because the patient continued to be intolerant to both oral solids and fluids, dimenhydrinate was replaced with prochlorperazine as per protocol on the day following her admission; nitrofurantoin was also changed to ampicillin and gentamycin, as a consequence of the patient’s persistent nausea and vomiting.

On the third night, the patient began to complain of soreness in her neck, and on the following morning the patient became agitated, demanding to be discharged against medical advice, believing she would recover spontaneously at home. The patient’s husband found her unusually anxious and he did not want her to be discharged, as she was still dependent on intravenous fluids. She continued to complain of neck stiffness, but had no limits to her range of motion, physical exam was unremarkable and without altered mental status. She was haemodynamically stable, afebrile, her complete blood count and electrolytes were normal. In the hour that followed, she experienced increasing difficulty answering questions and following commands, though at no time did she lose consciousness. For these brief periods, her breathing would intermittently also become stridorous, indicating her vocal cords were briefly paralysed by a laryngospasm. During these moments, she would extend her neck and develop uncontrollable episodes where she would roll back her eyes with a fixed upward gaze. Neurology was involved and she was diagnosed as having an oculogyric crisis secondarily to prochlorperazine. All her symptoms resolved within minutes of receiving 50 mg diphenhydramine intravenously and the prochlorperazine was discontinued.

Following this, the patient had a complex medical course, as her intolerance to oral intake persisted. She declined nasogastric feeds, eventually required total parenteral nutrition (TPN), and though her nausea gradually improved she continued to have limited oral intake until delivering her child. Her symptoms resolved completely immediately following her delivery and she has not experienced any further episodes of dystonia or akathisia.

Discussion

We report a case of an oculogyric crisis occurring in a young primigravid female treated with prochlorperazine for hyperemesis gravidarum. Although one can expect between 50 and 90% of women can develop nausea and vomiting in pregnancy, only 0.5% of patients will develop a severe enough disease that will result in weight loss, ketonuria, dehydration and electrolyte imbalances requiring hospitalisation [3]. Phenothiazines, and thus prochlorperazine, were given a I-A rating by the Society of Obstetricians and Gynaecologist of Canada clinical practice guidelines based on the results of several studies and clinical trials, where they significantly improved nausea and vomiting without conferring any additional teratogenic risk to the foetus [4]. These guidelines, however, do not take into account what other side effects these medications can have on the patient.

We want to emphasise in this report how easily akathisia can be missed in a patient anxious to be discharged. While one report found that 16% and 4% of patients admitted to the emergency department developed akathisia and dystonic reactions respectively to prochlorperazine [1], this phenomenon is very infrequently seen in obstetrics, as only a fraction of pregnant patients will develop akathisia and dystonia concurrently with hyperemesis gravidarum [6, 9]. While the risk of developing NMS has been linked with male gender, loading dose and dehydration, no statistical difference has been found with the dosage or gender of patients developing akathisia and dystonia in response to prochlorperazine [1, 7, 10]. The question as to whether the physiological and endocrinological changes that occur in pregnancy predispose women to developing these reactions is explored in an excellent review by Wright [10]. The patient’s presentation was particularly unusual not only in its severity, but also because the patient did not fit any of the classical expectations as to what would expose someone to the risk of NMS; this includes sex, dehydration, since she had been receiving IV fluids, and loading dose, as she had received a low potency neuroleptic over several days.

Both the rare and initially unimpressive nature of this event made it easy to dismiss the patient’s initial presentation and this could have led to her discharge with potentially disastrous consequences. While prochlorperazine has previously been reported to cause dystonia, in the context of viral infections and as a result, prochlorperazine’s use was restricted in children [2, 8], it is unclear if the patient’s initial presentation with a urinary tract infection contributed to her subsequent response to prochlorperazine.

While the eventual development of the oculogyric crisis made for a rapid diagnosis and was straightforward to treat with 50 mg diphenhydramine and the discontinuation of the prochlorperazine, we believe it is important to maintain a high degree of suspicion for complaints of muscular pain and stiffness and uncharacteristic changes in behaviour, as these may precede a focal dystonia that can progress into life-threatening conditions such as laryngospasms and NMS.