Management of a complex patient – intravenous olanzapine use

Case report

We report a case of a 55-year-old Samoan divorced father of four adult children, referred to a metropolitan adult acute psychiatric unit on an Assessment Order (MHA Vic, 2014) from an inner city corrections facility after serving a 3-year sentence for aggravated burglary. His documented mental state on referral included that of several days of limited oral intake, insomnia, disorganised behaviour, namely smearing of faeces and saliva on walls, digital penetration of his anus, clogging of toilet with clothes resulting in flooding, marked agitation and aggressive behaviour, requiring a period of management in the prison lockdown facility. The patient required hosing down and was treated with pepper spray in the prison cell before his extraction and transport to a metropolitan psychiatric inpatient unit. Given his history of aggravated assault and florid psychosis on presentation, the patient was admitted to the seclusion area. Overnight, it was reported that the patient remained impulsive, aggressive, verbally abusive, spitting, throwing objects at staff and perplexed, with intermittent yelling of ‘I’m going to paradise’. Of note, his Glasgow Coma Scale (GCS) fluctuated overnight.

On consultant psychiatrist review the following day in the acute psychiatric inpatient unit, it was noted that the patient had multiple haematomas on his forehead, maxillae, bilateral periorbital region, chest, abdomen and bilateral lower limbs. There were also multiple lacerations over his body including his forearms, thighs and feet. It was then revealed that, 1 week before his arrival on the ward, he had had a 6-day admission to the surgical unit of another metropolitan hospital following a psychotically driven incident in which he smashed and destroyed a toilet bowl and sink in the corrections facility. He received a surgical repair of multiple full thickness lacerations on his left forearm, left thigh and toe. He was then transferred back to the corrections facility and was commenced on oral olanzapine for ‘disturbed mental state’, which the patient was not compliant with.

Urgent physical work up and limited physical examination (due to his highly aroused state) on the psychiatric inpatient ward revealed multiple medical concerns. The patient had a prolonged QTc of 490 msec on electrocardiogram (ECG). A blood test also showed acute kidney injury in which his estimated glomerular filtration rate was 35.

Given the patient’s fluctuating GCS and diffuse haematomas, a pan-body computed tomography (CT) including a CT brain, was requested following consultation with the trauma team. Due to the patient’s acute arousal state and the urgency of the scan, he was required to be anaesthetized and intubated to facilitate performance of the scan. Imaging results of note showed extensive bilateral pulmonary embolism in the right and left main pulmonary arteries (Figure 1), foreign body in the distal sigmoid colon and T11 spinous process (Figure 2) and T12 end plate fractures (Figure 3). There was also unilateral below-knee deep vein thromboses on subsequent lower limbs ultrasound.

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Figure 1.

CT angiogram thoracic aorta: there is a filling defect within the terminal right main pulmonary artery with filling defects extending into segmental and subsegmental right upper, middle and lower lobe pulmonary arterial branches. There is also a filling defect within the left lower lobe main pulmonary artery with extension into segmental and subsegmental left lower lobe pulmonary arterial branches. There are also filling defects within segmental and subsegmental left upper lobe pulmonary arterial branches including lingular branches.

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Figure 2.

CT thoracic and lumbar spine: there is also a horizontally oriented minimally separated fracture through the spinous process of T11 that does not extend into the lamina bilaterally.

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Figure 3.

CT thoracic and lumbar spine: multiplanar images were obtained. There is a fracture through the superior endplate of the T12 vertebral body with extension into the anterior cortical margin and minimal angulation across the superior endplate. The fracture does not extend into the posterior elements.

The patient’s physical health needs continued to escalate as his medical review progressed in the psychiatric ward. It was obvious that the patient was acutely psychiatrically unwell and required immediate treatment for his mental illness, which would include administration of parenteral antipsychotic medications, as he was refusing any oral treatment. However, commencement of psychotropic treatment was restricted by the prolonged QTc, impaired renal function and risk of bleeding with intramuscular injection of antipsychotic medication as he was to commence on therapeutic anticoagulation for his extensive bilateral pulmonary embolism. His other medical needs included that of intravenous (IV) fluid therapy for pre-renal acute kidney injury and monitoring of multiple lacerations.

After extensive discussions with multiple specialties, a consensus was reached for the patient to be managed acutely in the intensive care unit (ICU). The patient’s care was subsequently transferred to the ICU team with ongoing input from the consultation-liaison psychiatry team. The patient was sedated and mechanically restrained during his initial stay in ICU. Due to the complex nature of his psychiatric and medical conditions, on balance of the risk and benefit of his illness, the decision was made to administer IV olanzapine to treat his mental illness and its associated behaviours in a timely fashion. He was commenced on IV olanzapine 10 mg three times a day. ¹ He received 24-hour cardiac monitoring for risk of further QTc prolongation. The patient was also commenced on therapeutic subcutaneous clexane for bilateral pulmonary embolism. On day 1 in the ICU, the patient developed acute ECG changes characterised by inferolateral leads ST depression and T-wave inversion, associated with troponin rise to 35. That was attributed to right heart strain from his pulmonary embolism. The patient was given glyceryl trinitrate infusion. On day 4 of his admission, the patient was transferred to the general medical ward as his medical health stabilised. IV olanzapine use was continued on the general medical ward. On day 6 of admission, in view of the ongoing severity of his psychosis with no significant improvement in his mental state and high risk behaviours, in spite of therapeutic dose of IV olanzapine, for instance ongoing commanding auditory hallucination to kill self, which the patient intended to act on, and grandiose delusions of being sent by the ‘Heavenly Mother to Earth’ for a special mission, the consultation-liaison psychiatry team made an application for an urgent electroconvulsive therapy (ECT) hearing. ² The ECT application was granted, and patient received a total of 11 ECT treatments. Of note, on initial admission to ICU, urgent ECT was considered. However, due to the patient’s cardiac compromisation secondary to extensive bilateral pulmonary embolism, this was deemed unsafe by the medical team. His medical complications improved with appropriate treatment, which enabled subsequent administration of ECT. On day 10 of his admission, the patient’s medical conditions improved further, and he was transferred back to the psychiatric unit. His mental state had also improved, and he was accepting of oral medications. The patient received the remainder of his care in the psychiatric ward. After a 47-day inpatient stay in which he made a good recovery, the patient was discharged on a community treatment order with community mental health team follow-up to a supported accommodation facility.

Discussion

The authors would like to address the use of IV olanzapine in this clinical scenario. The immediate-release intramuscular formulation is Food and Drug Administration (FDA)-approved for acute agitation related to schizophrenia and bipolar 1 mania. ³ However, the FDA has not approved IV olanzapine use for acute agitation associated with schizophrenia and bipolar disorder. There is no current prescribing guideline available. A recent expert consensus publication by Garriga et al. in assessment and management of agitation in psychiatry has suggested that ‘intravenous treatments should be avoided’. ⁴ Nonetheless, there has been increasing use of IV olanzapine in the emergency department (ED) in management of acutely agitated patients and its use has gained favour in ED patients who require intravenous access in the treatment of their condition and to avoid excessive needlesticks in patients. ⁵ In fact, IV olanzapine has been increasingly recognised as effective and safe for use in the ED setting. ⁶ It is replacing IV haloperidol, as IV olanzapine is associated with lower risk of extrapyramidal side effects and cardiac arrhythmia.^7,8 A randomised trial from Australia conducted with agitated patients concurrently receiving titrated midazolam indicated that IV olanzapine may be administered safely, with safety and efficacy profiles comparable to those of IV droperidol. ⁹ A further study conducted by Cole et al. showed the safety profile was favourable for both intramuscular and IV olanzapine use for patients in the ED. ¹ Their findings significantly supported the findings of other published literature indicating the safe use of IV olanzapine in the ED. Other side effects of IV olanzapine include that of over-sedation and respiratory depression, namely hypoxia requiring intubation and QTc prolongation. However, there was no current evidence of clinical significance or cases reported of an olanzapine-associated cardiac event of torsade de pointes. It has been argued that ECG monitoring was not required. ⁶ Admittedly, the literature to date indicating the safe and effective use of IV olanzapine is from studies conducted mainly in the ED environment, yet in our case of multiple complexities, the use of IV olanzapine was necessary for the initiation of treatment of the patient’s mental illness and management of his acute agitation associated with his manic psychosis in the ICU setting and on the medical ward.

In conclusion, there is some evidence of efficacy and safety to support the use of IV olanzapine in the ED, but very little, to negligible, evidence outside of the ED. Until more data are available, IV olanzapine remains off-label use, and potential risks need to be weighed up against the benefits. Further research in this area would be beneficial.