SEARCH

SEARCH BY CITATION

Summary

  1. Top of page
  2. Summary
  3. Case report
  4. Discussion
  5. References

We describe the initial management and subsequent recovery of a 61 year-old male patient following attempted suicide by oral ingestion of a potentially fatal overdose of quetiapine and sertraline. Intravenous Intralipid® was given soon after initiation of basic resuscitation. There was a rapid improvement in the patient’s level of consciousness. No other clinical signs of drug toxicity were observed. Intralipid may have reversed the deep coma associated with ingestion and prevented other manifestations of drug toxicity occurring, thus expediting this patient's recovery.

Antidepressants and antipsychotics are often ingested in suicide attempts. There were 336 deaths attributable in part, or whole, to overdose of antidepressant drugs in England and Wales in 2006 [1]. Intensive care resources may be required for the stabilisation and subsequent treatment of patients due to the sedative nature of these drugs, especially when cardiorespiratory instability and other major organ involvement are present or anticipated. Currently, treatment options are limited to those which may reduce or delay absorption and thereafter measures intended to address the physiological disturbance caused by the toxic effects of the overdose [2]. In general no specific antidote is available.

Intravenous lipid emulsion is an effective treatment for cardiovascular collapse associated with local anaesthetic induced toxicity. Intralipid® (Fresenius Kabi, Runcorn, UK) appears to create an intravascular ‘lipid sink’ and may have the capacity to bind lipophilic drugs present at toxic concentrations. Such ‘lipid rescue’ may provide a useful treatment in the management of overdose associated with lipid soluble drugs.

Case report

  1. Top of page
  2. Summary
  3. Case report
  4. Discussion
  5. References

A 61 year-old male (67 kg, ASA II) presented to the Emergency Department following an overdose of quetiapine and sertraline. He was known to suffer from bipolar depression and had recently been discharged from a local psychiatric unit following treatment of a previous suicide attempt. He had taken 4.3 g of quetiapine and 3.1 g of sertraline at 08:30 h on the morning of admission. It was also understood that he had access to a supply of benzodiazepines. When he was found by his wife, he was unresponsive and an ambulance was called. Initially, paramedics assessed his Glasgow Coma Score (GCS) as 8 but during transfer to hospital his level of consciousness deteriorated. On arrival in hospital, 3.5 h after the presumed time of overdose, his GCS had decreased to 3. At that time he was spontaneously breathing at a rate of 18 bpm, with a Spo2 of 100% (receiving oxygen delivered at 10 l.min−1 via a mask equipped with a reservoir bag). He was hypotensive (88/64 mmHg) and in sinus rhythm with a pulse rate of 80 bpm. His core temperature was 34.4 °C. Arterial blood gas analysis revealed no acid-base disturbance (pH 7.33, Pao2 38.4 kPa, Paco2 7.1 kPa, base excess 1.5 mmol.l−1, bicarbonate 24.8 mmol.l−1, lactate 1.0 mmol.l−1). His serum sodium was 139 mmol.l−1, potassium 4.3 mmol.l−1, and glucose 6.9 mmol.l−1. An ECG showed normal sinus rhythm with no prolongation of the QT interval. Laboratory investigations including toxicology tests and sepsis screening were requested.

Airway patency was ensured with an oropharyngeal airway, oxygen treatment was continued, intravenous fluids and regular monitoring, including continuous ECG, were instituted and the local Poisons Centre was contacted. They advised that the opportunity to initiate activated charcoal therapy to reduce enteral absorption had been missed. Due to the possibility of benzodiazepine ingestion, flumazenil by infusion (400 μg.h−1) was recommended and commenced. Preparation to intubate the patient’s trachea was made with a simultaneous request to transfer the patient to the ICU. Given the patient’s deeply comatose state and the acknowledged lipophilic nature of both drugs, ‘lipid rescue’ was considered. Thirty minutes after admission to hospital and 4 h after the overdose, 20% lipid emulsion (Intralipid®, Fresenius Kabi) was administered intravenously as an initial bolus dose of 1.5 ml.kg−1 (100 ml), followed by an infusion of 6 ml.kg−1 (400 ml) over the next hour. A rapid and sustained increase in level of consciousness (GCS 9) occurred simultaneously with the Intralipid administration, resulting in restoration of protective airway reflexes to the extent that within 15 min of commencement of the Intralipid the oropharyngeal airway was no longer tolerated. The patient started opening his eyes to speech and localising to pain, and intubation was abandoned. Thereafter, spontaneous ventilation was maintained and no cardiovascular instability was observed. He was transferred to the High Dependency Unit, where his vital signs and neurological status were monitored overnight. All vital signs observations were recorded within normal ranges except body temperature, which returned to normal within 12 h after admission. A review of laboratory tests results showed no evidence of sepsis, renal or liver impairment. Blood paracetamol was estimated at 0.015 mmol.l−1 and salicylate was undetectable. Our laboratory confirmed the absence of benzodiazepines, but did not have the facility to detect or quantify sertraline or quetiapine levels. By 03:00 h the following day, less than 19 h after the self poisoning, the patient’s GCS had increased to 12. He was transferred to a medical ward a few hours later with GCS restored to 15. The patient was subsequently returned to the institution responsible for his continuing psychiatric care.

Discussion

  1. Top of page
  2. Summary
  3. Case report
  4. Discussion
  5. References

In the absence of specific therapeutic measures, the current recommendation from toxicology and poisons information centres for many antipsychotic or antidepressant drugs taken in overdose, including sertraline and quetiapine, is supportive therapy dictated by the patient’s clinical status [2]. Quetiapine is an atypical antipsychotic with its effect mediated via dopamine and serotonin receptor antagonism. It is rapidly absorbed by mouth and commonly causes sedation mediated via antihistamine activity at H1 receptors. Thus, it is often prescribed as a single bedtime dose and may be used to treat insomnolence. Quetiapine has a half life of approximately 7 h with peak plasma concentrations occurring about 2 h after ingestion. It has the potential to reduce the seizure threshold in response to other drugs. Quetiapine has been reported to have caused death at a dose of 10.8 g [3]. A recent audit of quetiapine overdose showed complications, including death, were more common than with other antipsychotics [4]. Sertraline is a selective serotonin reuptake inhibitor (SSRI) primarily used to treat clinical depression. It is also used in the treatment of obsessive-compulsive, panic and social anxiety disorders. In contrast to quetiapine, sertraline is absorbed more slowly, achieving peak plasma levels between 4–8 h after ingestion. It has a half life of 13–45 h. It is highly protein bound in plasma and has a high lipid partition co-efficient. Death has occurred following ingestion of 2.5 g. In contrast to tricyclic drugs, increased prescribing of SSRI’s is associated with an increase in fatal self-poisoning [5].

The role of lipid rescue in the treatment of local anaesthetic toxicity has achieved widespread acceptance. Animal studies during the past decade have established intravenous infusion of lipid emulsion as a highly effective treatment for cardiac arrest caused by overdose of bupivacaine and other local anaesthetics [6, 7]. Improvement in outcomes from local anaesthetic toxicity follows both pretreatment and simultaneous resuscitation with Intralipid [8]. The mechanisms responsible for the therapeutic effect of lipid infusion associated with local anaesthetic toxicity appear to involve both intracellular modulation and drug binding within the plasma, the so called ‘lipid sink’ effect. Lipid emulsions are used as a vehicle for a number of intravenous pharmaceutical agents and constitute an important element of total parenteral nutrition and would, therefore, appear to be without significant risk. Nevertheless, a review of the cautions that need to be exercised with lipid emulsion infusions is encompassed in a recent editorial [9].

Lipid rescue is a useful adjunct in the treatment of local anaesthetic-induced acute toxicity presenting with either neurological [10] or cardiovascular [11] sequelae or both [12, 13]. However, circumstances in which local anaesthetic toxicity manifests as cardiorespiratory arrest is unlikely to occur commonly. Application of the highest principles governing the teaching and practice of regional anaesthesia, with meticulous attention to safe technique, should ensure recourse to Intralipid for the treatment of an acute local anaesthetic induced event remains an infrequent necessity [14, 15]. In contrast, deliberate overdose is unpredictable, both in terms of the combination and dosage of the drugs consumed, however the underlying intention is that of self harm. Furthermore the frequency with which deliberate self harm through overdose of prescription drugs occurs provides a compelling justification to evaluate the efficacy of lipid rescue as an antidote [1, 16].

Preliminary animal studies using lipid emulsion in the treatment of toxicity from a variety of lipophilic drugs other than local anaesthetics have been conducted. These include clomipramine [17, 18], verapamil [19, 20], propranolol [21] and thiopentone [22]. Successful resuscitation of a patient following a potentially lethal overdose of bupropion and lamotrigine, using lipid rescue, has been reported. Lipid emulsion was administered when cardiac arrest had proved refractory to conventional treatment [23]. Given the successful outcome in a seemingly futile case, it is interesting to speculate whether, in retrospect, the authors would have considered earlier initiation of lipid rescue in the treatment of their patient.

Most notable in the treatment of our patient was the relatively rapid increase in level of consciousness occurring once Intralipid had been commenced, and the absence of cardiovascular or metabolic instability subsequently observed. The timing of the Intralipid fortuitously mirrored the predicted systemic uptake of the sertraline. The patient consumed 3.1 g which exceeds the dose known to have caused death, and we consider it is probable this dose would have caused more cardiac and vascular instability than was observed. It may be that progression to the full toxic effect was halted in a similar manner to that which occurred following early administration of Intralipid to a patient known to have received a toxic dose of local anaesthetic [24]. In this case the Intralipid is thought to have pre-empted progression to cardiac arrest.

Given the magnitude of the combined overdose of quetiapine and sertraline ingested by this patient, recovery following Intralipid administration appeared to be disproportionately rapid and without the complications that might have occurred. We believe the future application of lipid rescue may extend beyond its use as an antidote for local anaesthetic induced toxicity. If it were to establish a role in the treatment of intentional drug overdose involving lipid soluble drugs, it has the potential to provide a useful and cost effective early treatment option to the benefit of many more patients.

References

  1. Top of page
  2. Summary
  3. Case report
  4. Discussion
  5. References