\\ \\ \\ \\ Common Complications ---- ===== Cardiac Arrest ===== Cardiac arrest secondary to poisoning normally occurs early, when peak serum drug levels are expected, however may be delayed in the case of sustained release preparations. For the most part, resuscitation of patients should follow standard advance life support protocols. There are however a few specific considerations in the poisoned patient: \\ \\ **Prolonged resuscitation**: Poisoned patients are usually healthy before cardiac arrest occurs and the toxic effects are likely to be reversable. Provision of prolonged CPR enables time for redistribution of toxins and time for interventions to be effective. Survival with good neurological outcomes, even after hours of CPR is reported. \\ \\ **Extracorporeal membrane oxygenation (ECMO)**: In refractory cardiac arrest, especially when cardiac toxins are involved then discussion with the local ECMO team and clinical toxicologist should be undertaken. \\ \\ **Antidote provision**: In most cases of poisoning induced cardiac arrest, antidotal therapy is unlikely to have a significant influence. There are however a few situations where they are indicated e.g. sodium bicarbonate in TCA toxicity, magnesium for drug induced Torsades de Pointes. Consult the drug specific monographs, as well as your local toxicology service, for specific advice. ---- ===== Aspiration ===== Aspiration of stomach contents into the lungs is a common risk in patients following poisoning. Typically, this follows ingestion of drugs that are sedating and therefore impair the normal protective airway reflexes or are emetogenic. Other risk factors include increasing age, seizures, delayed presentation and ingestion of agents such as hydrocarbons, herbicides or pesticides. \\ \\ **Aspiration pneumonitis** refers to a chemical injury to the lung parenchyma secondary to the acidic stomach contents and is significantly associated with increased mortality and length of stay in the poisoned patient. \\ \\ It is important to recognise the difference between **aspiration pneumonitis** and **aspiration pneumonia**, as their management differs. \\ \\ With **aspiration pneumonitis**, symptoms generally develop rapidly (within a few hours of aspiration event). Chest x-ray changes may appear similar an aspiration pneumonia but clinically the patient often does not present as unwell as would be expected if the x-ray changes were infection related. Symptoms secondary to pneumonitis tend to improve quickly – usually within 24-48hrs. Treatment is symptomatic with the provision of supplemental oxygen to maintain oxygenation and chest physiotherapy. \\ \\ **Aspiration pneumonia** occurs due to aspiration of organisms from the oropharynx. Onset of symptoms is more gradual. Aspiration pneumonia can develop from aspiration pneumonitis, with those taking gastric acid suppressive therapy being at increased risk of this. In addition to the treatment for aspiration pneumonitis, these patients will also require antibiotic therapy. In some cases, differentiating between the two entities can be difficult and the provision of antibiotics for 24-48hrs can be considered. If the patient has shown a significant improvement in this time, then pneumonitis is the more likely diagnosis and the antibiotics can be discontinued. ---- ===== Seizures ===== There are many toxins that may lead to seizures. Seizures may occur as a direct result of drug toxicity or be secondary – such as in the case of drug induced hypoglycaemia or hypoxia. It is also important to remember that seizures may occur as a result of drug withdrawal states e.g alcohol, benzodiazepines. \\ \\ In general drug induced seizures are short and self-limited, however rarely, status epilepticus may develop and is usually due to directly pro-convulsant agents, rather than secondary effects. The mechanisms of seizure production from directly proconvulsant drugs include: GABA antagonism (e.g. flumazenil), g lycine antagonism (e.g. strychnine), Na+ Channel blockade (e.g. lignocaine ), a denosine receptor antagonism (e.g. theophylline ), d isturbance of energy metabolism (e.g. salicylates , isoniazid).\\ \\ There are also agents that cause seizures but the mechanism by which these occur is unclear (e.g. organochlorines ). ==== Treatment ==== Hypoglycaemia should always be considered as a possible cause of seizure in poisoning. Urgently check a blood sugar and correct hypoglycaemia (<4mmol/L) with intravenous glucose * Adults:**50ml of 50% dextrose**, by slow injection, via a large peripheral vein OR **250ml of 10% dextrose**, via slow injection, via a large peripheral vein * Children:**2.5ml/kg of 10% dextrose** by slow injection, via large peripheral vein Most seizures that occur secondary to poisoning will be short and self-limiting and therefore do not require any specific treatment. However, if seizures are prolonged (more than a few minutes) or recurrent then treatment to terminate the seizure or prevent recurrence should be given. \\ \\ First line treatment should be with a benzodiazepine. Common options include: * **Midazolam 5 to 10mg (child: 0.15mg/kg up to 10mg)** intravenously or intramuscularly, over 2 to 5 minutes, repeat once at 5 minutes if seizures continue OR **Diazepam 5 to 10mg (child: 0.1 to 0.3 mg/kg up to 10mg)**, intravenously, over 2 to 5 minutes, repeat once at 5 minutes if seizures continue. If seizures fail to terminate, or continue to recur, despite the above treatment then consultation with a clinical toxicologist should be sought. Appropriate second line agents include: * **Levetiracetam 20mg/kg up to 2g** intravenously over 15 minutes.**Phenobarbital 20mg/kg up to 2g (1g in a child)** intravenously over 20 minutes. ** Note: Phenytoin should not be used, it has been shown to both be ineffective in drug induced seizures and possesses sodium channel blocking action which may increase the toxicity of some agents. ** Isoniazid (INH) is a special case which requires specific management with pyridoxine (vitamin B6). Refer to the isoniazid monograph for more information. ---- ===== Rhabdomyolysis ===== Rhabdomyolysis in the setting of poisoning most commonly occurs due to prolonged sedation and its resultant pressure induced injuries. Less frequently it can be induced by hyperthermia, stimulant drugs, prolonged seizures or direct toxin effect (e.g. snake venom induced myotoxicity). \\ \\ Rhabdomyolysis is characterised by myoglobinuria, muscle pains and swelling. It can be confirmed by measuring a serum creatine kinase level or by the detection of myoglobin in the urine. \\ \\ A high index of suspicion should be maintained in patients presenting with an altered level of consciousness (especially if the presentation is delayed) as they are unable to complain of the associated symptoms. Compartment syndrome can easily be missed in a patient who is unconscious and examination specifically looking for evidence of this should be undertaken in those at risk. \\ \\ Complications include hyperkalaemia, hypocalcaemia, acute kidney injury and permanent tissue injury. \\ \\ The principles of treatment include: * Pressure cares (pressure relieving mattress, regular patient repositioning) * Intravenous fluids to maintain a urine output of 1 to 2 ml/kg * Monitoring and treatment of electrolyte derangements \\ Patients with worsening renal function/urine output, despite the above measures should be referred to a nephrologist as they may require dialysis. If compartment syndrome is suspected, urgent surgical referral is required. ---- ===== Thrombosis ===== Thrombosis and thromboembolism are risks for all hospitalised patients. Poisoned patients, particularly those with sedative ingestions are at especially high risk given their immobility. Dehydration due to the inability to drink increases the risk further. \\ \\ Consider the risk of thrombosis in each patient and in those that are at risk (and do not have a contraindication) provide appropriate thromboprophylaxis. The choice of agent will depend on your local guidelines but can include agents such as low molecular weight heparin, unfractionated heparin and mechanical devices (e.g. compression socks). \\ \\ Patients who present in a delayed fashion may already have thrombosis by the time they arrive in hospital, consider investigation for deep vein thrombosis (DVT) in those that have evidence of a long-lie (rhabdomyolysis, pressure injuries, hypothermia). ---- ===== Hyperthermia ===== Hyperthermia (>39^oC or rapidly rising) is a potentially life-threatening drug effect. The degree of risk is related to the height of the absolute temperature as well as the duration of the elevation. \\ \\ Three toxidromes are commonly associated with hyperthermia: Sympathomimetic: amfetamines and related drugs, theophylline, caffeine. Serotonergic: selective serotonin re-uptake inhibitors (SSRIs), monoamine oxidase inhibitors MAOi. Neuroleptic malignant syndrome: haloperidol, paliperidone. \\ \\ Irrespective of the precise cause, the principles of management are the same and involve active cooling, suppression of shivering and control of agitation. Treatment options include: * **Cool intravenous fluids (4^o C)**: hyperthermic patients are often fluid deplete and using cooled fluids for resuscitation (e.g. starting with a 20ml/kg bolus) can help reduce temperature as well as replace fluid losses. * **Sedation**: Increased muscle activity will drive further temperature rises. In the agitated patient, especially those affected by stimulants, sedation may be all that is required to treat hyperthermia. Good options include droperidol 10mg Intravenously/intramuscularly repeated once at 15 mins if needed or a benzodiazepine (midazolam 1mg intravenously every 5 minutes or diazepam 2mg IV every 5 minutes until the patient is calm). * **Other cooling measures**: ice pack to groin and axillae, tepid sponging and fanning, cool mats or blankets. If the above measures fail or the temperature exceeds 41^oC, then more aggressive measure including intubation with paralysis and external cooling (e.g. haemodialysis, ECMO) should be considered and discussed with your toxicological and intensive care services. ---- ===== Further Reading ===== - Isbister GK, Downes F, Sibbritt D, Dawson AH, Whyte IM. Aspiration pneumonitis in an overdose population: frequency, predictors, and outcomes. Crit Care Med 2004;32(1):88–93. {{:wikitox:aspiration_pneumonitis_in_an_overdose_population_frequency_predictors_and_outcomes.pdf|PDF}} - Jones CL, Koios J. Algorithm for the treatment of status epilepticus: an Australian perspective. Intern Med J 2016;46(4):500–3 {{:wikitox:internal_medicine_journal_-_2016_-_jones_-_algorithm_for_the_treatment_of_status_epilepticus_an_australian_perspective.pdf|PDF}} - Lee T, Warrick BJ, Sarangarm P, Alunday RL, Bussmann S, Smolinske SC, et al. Levetiracetam in toxic seizures. Clin Toxicol (Phila) 2018;56(3):175–81 {{:wikitox:levetiracetam_in_toxic_seizures.pdf|PDF}}