Airway and ventilation management

Problems should not be created by treatment. Gastric lavage should not be undertaken unless the patient has ingested a significant toxin in significant amounts within the past hour. There are very few indications for gastric lavage. Gastric lavage should not be performed in the fully conscious or in the less-than-fully conscious patient, without prior securement of the airway with rapid sequence endotracheal intubation. Likewise, activated charcoal should not be administered by oro/nasogastric tube in a patient who is less-than-fully conscious, irrespective of the interval since ingestion. The risk of aspiration pneumonitis in these circumstances is significant. If activated charcoal is to given by naso/orogastruc tube, confirm it is in the stomach, not the lungs, prior to instilling the charcoal.

Drug-induced asystole

Infusions of KCl are hazardous. Molar solutions of KCl are in common use in intensive care units especially after cardiac surgery. They should not be available for regular ward use. An inadvertent IV bolus of potassium can cause asystole. Note that a 1 mL bolus of molar KCl (1 mmol) in a 10 kg child will theoretically raise the serum concentration by 2.5 mmol L^–1 and cause immediate asystole.

Immediately acting treatment (within seconds) for hyperkalaemia is either 10% calcium chloride IV 0.2 mL kg^–1 (or equivalent) or IV sodium bicarbonate 1 mmol kg^–1 or both. Calcium antagonises the cardiac effects of potassium on the heart, while the bicarbonate lowers the serum concentration of potassium by a small amount. Better treatments of rapid onset (within minutes) are glucose 0.5 g kg^–1 IV (e.g. 5 mL kg^–1 of 10%) plus insulin 0.05 units kg^–1 or salbutamol 0.25 mg kg^–1 by aerosol or both. Slow treatment (within hours) is by resonium, oral or rectal, 0.5–1 g kg^–1.

Drug-induced bradycardia

Organophosphate and carbamate poisoning with bradycardia should be treated with atropine – repeated doses of 20–50 mcg kg^–1 every 15 minutes or until secretions are dry and an acceptable heart rate is restored. In organophosphate poisoning (but not carbamate), pralidoxime can reactivate cholinesterase. The dose is 25 mg kg^–1 IV over 15–30 minutes then 10–20 mg kg^–1 per hour for 18 hours or more.

Bradycardia induced by β-blocker poisoning is treated with glucagon 7 mcg kg^–1 IV then 2–7 mcg kg^–1 min^–1. This is the preferred antidote because it stimulates non-catecholamine cAMP. Isoprenaline 0.05–3 mcg kg^–1 min^–1 by infusion may be used but it may cause β₂-induced hypotension and should not be used if hypotension is pre-existing. Alternatively, an infusion of adrenalin (epinephrine) at 0.05–1 mcg kg^–1 min^–1 may be used.

Digoxin induced bradycardia may be treated with 1 Digoxin Fab antibody in a dose of 10 vials per 25 of 0.25 mg tablets or per 5 mg elixir ingested. At steady state, the number of vials is calculated as serum digoxin (ng mL^–1) × (kg)/100.

Drug-induced tachyarrhythmias

The preferred treatment is a benzodiazepine such as diazepam or midazolam in doses that do not depress CNS function. Other treatments are the ultrashort-acting cardioselective β₁ blocker esmolol IV 500 mcg kg^–1 over 1 minute and then 25–200 mcg kg^–1 min^–1 by infusion. Treatments such as intravenous adenosine and DC shock are not likely to be effective because the toxic drug effect will be persistent. Calcium channel blockers such as verapamil may cause severe hypotension and should not be given.

Drug-induced hypertension

Hypertension may occur with poisoning by cocaine, amphetamine and similar substances, which cause vasoconstriction, tachycardia and arrhythmias. Benzodiazepines are the preferred treatment. Another alternative is a smooth muscle dilator such as sodium nitroprusside IV 0.5–2 mcg kg^–1 min^–1, but its use mandates intra-arterial monitoring. Another choice is phentolamine IV 0.05–0.1 mg kg^–1 and then an infusion of 5–50 mcg kg^–1 min^–1. Propranolol, a non-selective β-blocker is contraindicated because it may paradoxically worsen hypertension when β₂-adrenoreceptors are blocked.

Drug-induced ventricular tachycardia (VT) and fibrillation (VF)

Haemodynamically stable VT can be treated with anti-arrhythmic agents. Typical drug causes are tricyclic antidepressants, cocaine and amphetamines. These cause a monomorphic VT by increasing the QRS interval. Treatment should be sodium bicarbonate, especially in cases of tricyclic poisoning. Both components of the sodium bicarbonate contribute to its antidotal effect – the sodium counters the sodium channel blockade effect of the drugs and the alkalosis reduces bioavailability. Induction of respiratory alkalosis is also beneficial. The preferred antidysrrhythmic agent is lidocaine. Phenytoin is no longer recommended. Polymorphic VT (torsade de pointes) of any cause should be treated with magnesium 25–50 mg kg^–1 IV.

Pulseless VT or VF require DC shock. The use of adrenaline (epinephrine) in this situation should be limited to 10 mcg kg^–1 boluses while higher doses which may cause recurrent VF or VT should be avoided. Propranolol is contraindicated.

Drug-induced shock

Shock may result from drugs that cause depression of myocardial contractility, vasodilatation or loss of intravascular volume, or combinations of these. An extreme rise in peripheral vascular resistance may also lead to myocardial failure. Whenever possible preload, contractility and afterload should be measured via a central venous line.

Preload deficiencies (hypovolaemia) are corrected with volume administration, titrated against blood pressure, right heart filling pressure and against pulmonary artery wedge pressure.

Infusion of dopamine is a suitable inotropic agent in doses of approximately 5–15 mcg kg^–1 min^–1, although higher doses may be needed or other inotropic drugs added. If central access is not possible, infusion of dobutamine in a similar dose may be given via a peripheral venous access, at least in the short term. Other inotropic agents are infusions of calcium (0.03–0.1 mL kg^–1 hr^–1 of 10% CaCl₂, i.e. 3–10 mg kg^–1 hr^–1), milrinone (50 mcg kg^–1 loading dose then 0.375–0.75 mcg kg^–1 min^–1) and glucagon. It is desirable to measure cardiac output or to assess contractility with echocardiography.

Vasodilatation is treated with an α-adrenergic agent such as noradrenaline (norepinephrine) infusion (0.05–1 mcg kg^–1 min^–1) in the higher dose range. Other such agents are phenylephrine (1-5 μg kg^–1 min^–1) and metaraminol (0.05–1 mcg kg^–1 min^–1). Vasoconstriction is also obtained with vasopressin infusion (0.002–0.01 units kg^–1 min^–1).

In selected circumstances, cardiac output can be supported with ventricular assist devices, extra-corporeal membrane oxygenation (ECMO) or intra-aortic balloon pumping, although the last named requires intrinsic cardiac rhythm. These techniques are sometimes used in toxicological emergencies in centres that use these techniques for cardiac surgery. They are only indicated when standard supportive measures are insufficient but the situation is recoverable, and organ damage, particularly brain damage, has not occurred. The principal risks with such techniques are haemorrhage, infection and mechanical failure.

Respiratory failure and bulbar palsy

Many venoms contains neurotoxins. Respiratory and airway support may be required for a prolonged period. Although paralysis caused by some animals, e.g. blue-ringed octopuses, may be relatively brief, lasting perhaps several hours (if support is given), paralysis caused by some snake and funnel-web spider venoms may be lengthy. For example, a child considered to have been bitten by a Rough-scaled snake remained ventilator dependent for 10 weeks, although antivenom administration in that case was delayed.²

Coagulopathy and haemorrhage

Snake-bite-induced coagulopathy, and haemorrhage and shock, may be prolonged and may not respond readily to administration of antivenom and clotting factors. Antivenom alone does not per se restore normal coagulation. In the presence of haemorrhage, it is prudent to administer clotting factors if normal coagulation is not restored soon after antivenom administration, since serum levels of coagulation factors are not restored by liver function for approximately 6 hours after complete consumption of clotting factors during DIC. In the absence of any ability to measure the serum concentrations of venom components it is difficult to judge how much antivenom is required when the sole effect of venom is coagulopathy. Hitherto recommended neutralisation doses of antivenom have been found inadequate in canine and human plasma models of envenomation and coagulopathy.^3,4

Rhabdomyolysis

Some envenomations cause rhabdomyolysis with implications for renal function, electrolyte disturbances (hyperkalaemia, hypocalcaemia) and muscle weakness. This is expected after envenomation by certain snakes (e.g. tiger snakes, black snakes, Beaked sea snake) and funnel-web spiders, particularly if antivenom therapy is inadequate or delayed. Myocardial muscle may be involved.

Cardiac dysrhythmias

Cardiac dysrhythmias have been observed after envenomation by some creatures. The venom of funnel-web spiders and that of the Irukandji jellyfish cause massive release of endogenous catecholamines, which may be responsible for tachydysrhythmia, stress-induced (Takotsubo) cardiomyopathy and ischaemia. The venom of the Box jellyfish (Chironex fleckeri) can kill rapidly – the exact cause is still unknown but it may be related in part to dysrhythmia caused by hyperkalaemia secondary to haemolysis, or rapid onset of myocardial cytolysis caused by cell membrane pore-forming toxins.⁵

Hypertension

Severe hypertension may occur after bites from funnel-web spiders and after stings from jellyfish causing Irukandji syndrome. This is in part caused by release of endogenous catecholamines. Treatment could be with vasodilators, α-and β-adrenergic blockade. The infusion of magnesium may ameliorate the components of the Irukandji syndrome.⁶

Adverse reactions to antivenom

The treatment of some envenomations by antivenom may be complicated by reactions to antivenom. Adverse reactions to Australian snake antivenoms occur in approximately 8–13% of cases – which is relatively small compared to some overseas manufactured antivenoms, but not insignificant. It is thus prudent to prevent anaphylaxis by premedication with subcutaneous adrenaline (epinephrine) 0.25 mg for an adult, 5–10 μg kg^–1 for a child. This recommendation stems from high-level scientific evidence: A prospective, double blind, randomised, placebo-controlled trial of 0.25 mg of subcutaneous adrenaline as premedication for snake antivenom in Sri Lanka found that subcutaneous adrenaline reduced the reaction rate from 43% to 11% (p = 0.0002) and reduced the severity of reactions.⁷ Thus, although adrenaline has a potential to cause cerebral haemorrhage in a snake-venom induced coagulopathic state when given intravenously or intramuscularly, but not when given subcutaneously,⁸ it should be administered. This controversial subject was subject to a systematic review,⁹ which concluded: ‘If clinicians believe local factors do not justify routine adrenaline, then they should test their belief in a randomised trial’. In contrast, more high-level evidence, a randomised, double blind, placebo-controlled trial of promethazine as a premedication for snake antivenom in Brazil¹⁰ did not alter the reaction rate (25% placebo, 24% promethazine) and was thus not beneficial. Moreover, the effects of promethazine, hypotension and CNS obtundation might exacerbate the illness caused by envenomation. Promethazine is therefore contraindicated as a premedication.

Pressure-immobilisation bandage

Application of a pressure-immobilisation bandage is essential in the early management of selected envenomations. Elasticised bandages maintain pressure better than non-elasticised bandages. Delay in application or premature removal of a bandage may severely compromise resuscitation. Envenomations by snakes, funnel-web spiders, blue-ringed octopuses, and cone shells all warrant application of a bandage. The venoms of these creatures contain components that cause rapid onset of paralysis. The bandage serves to maintain venom at the bite or sting site¹¹ and hence prevents venom access to the general circulation and exerting systemic effects.

Unfortunately, application of a bandage is not always performed well or in a timely manner both before and after arrival of the victim at hospital. A critically ill victim should have a bandage applied in the Emergency Department, if one is not already in place on arrival and it should not be removed until antivenom, if indicated, has been administered.