Learn — Emergency drugs, poisoning & antidotes

12 notes · 66 questions on the topic

Cocaine toxicity

Cocaine is a sympathomimetic that blocks the presynaptic reuptake of noradrenaline, dopamine and serotonin, and at the same time a local anaesthetic that blocks fast sodium channels in the myocardium. That double action explains the whole toxic picture at the bedside: an agitated, hypertensive, tachycardic, hyperthermic patient who can infarct a normal coronary artery through vasospasm and can widen the QRS like any sodium-channel blocker.

Mechanism: reuptake blockade at the noradrenaline, dopamine and serotonin transporters produces the sympathomimetic storm, while myocardial sodium-channel blockade widens the QRS and is treated with sodium bicarbonate rather than with more sedation.
Presentation: agitation, dilated but reactive pupils, drenching sweat, hypertension, tachycardia, hyperthermia, seizures, chest pain from coronary vasospasm, and stroke or intracerebral haemorrhage in a young adult.
Benzodiazepines are first-line for everything: diazepam 5 to 10 mg or lorazepam 2 to 4 mg intravenously, repeated until the patient is calm, because sedation itself lowers the blood pressure, the heart rate and the temperature.
The adverse effect that decides nursing action is hyperthermia: a core temperature of 40 degrees Celsius or more predicts death and calls for active cooling with cold fluids, exposure, evaporative cooling and ice packs, not for antipyretics, which do not work here.
There is no antidote. The specific agents are phentolamine 1 to 5 mg intravenously or nitroglycerin for persistent hypertension and ischaemic chest pain, and sodium bicarbonate 1 to 2 mEq/kg when the QRS is wider than 100 to 120 ms.
Monitoring: continuous ECG for QRS width and arrhythmia, core temperature, serial troponin, creatine kinase and creatinine for rhabdomyolysis with acute kidney injury, and hourly urine output with intravenous crystalloid to keep it flowing.
The contraindication to remember is a beta-blocker given alone in acute toxicity: blocking beta-2 vasodilatation leaves alpha-mediated vasoconstriction unopposed and worsens the hypertension and the coronary spasm.

Acetaminophen (paracetamol) toxicity

Paracetamol is safe at therapeutic doses because most of it is conjugated with glucuronide and sulphate, and the small fraction oxidised by CYP2E1 to the reactive metabolite NAPQI is neutralised by glutathione. In overdose the conjugation pathways saturate, glutathione is exhausted, and free NAPQI binds hepatocyte proteins to produce centrilobular necrosis, so the patient looks completely well on the first day and is in fulminant hepatic failure on the third.

Toxic threshold: a single ingestion of 150 mg/kg or more, about 7.5 to 10 g in an adult; the maximum therapeutic adult dose is 4 g in 24 hours, and no more than 2 to 3 g a day in chronic alcohol use, malnutrition, low body weight or liver disease.
Four stages: 0 to 24 hours of nausea, vomiting and pallor or nothing at all; 24 to 72 hours of right upper quadrant pain with rising transaminases and INR; 72 to 96 hours of peak necrosis with jaundice, encephalopathy, hypoglycaemia, lactic acidosis and acute kidney injury; then recovery over 1 to 2 weeks, or death.
The 4-hour serum level plotted on the Rumack-Matthew nomogram decides treatment after a single acute ingestion; a level before 4 hours is meaningless, and the nomogram does not apply to staggered ingestion, modified-release preparations or an unknown time of ingestion, where treatment is started on the history alone.
Antidote: N-acetylcysteine, a glutathione precursor, given intravenously as 150 mg/kg over 60 minutes, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours, a total of 300 mg/kg over 21 hours; the oral regimen is 140 mg/kg loading then 70 mg/kg every 4 hours for 17 doses.
Timing is the whole battle: N-acetylcysteine is close to completely protective when started within 8 hours of ingestion, its benefit falls steeply after that, and it is still given beyond 24 hours if there is any evidence of liver injury or a rising INR.
Activated charcoal 1 g/kg, to a maximum of 50 g, is worth giving within 1 to 2 hours of ingestion and does not prevent N-acetylcysteine being given afterwards.
Monitoring: ALT and AST, INR or prothrombin time, creatinine, capillary and laboratory glucose, arterial pH and lactate. A rising INR is the earliest reliable marker of significant injury, and hypoglycaemia marks a failing liver.
Refer for transplant assessment by the King's College criteria: an arterial pH below 7.3 after fluid resuscitation, or the combination of INR above 6.5, creatinine above 3.4 mg/dL and grade III or IV encephalopathy.

Carbon monoxide poisoning

Carbon monoxide is a colourless, odourless gas that binds haemoglobin with roughly 200 to 250 times the affinity of oxygen to form carboxyhaemoglobin, which carries no oxygen and shifts the dissociation curve to the left so that the little oxygen carried is not released to the tissues. It also binds cytochrome oxidase and myoglobin, so the patient has cellular hypoxia and myocardial depression while the pulse oximeter, which cannot distinguish carboxyhaemoglobin from oxyhaemoglobin, reads a comfortable 98 per cent.

Sources in India: coal or charcoal burning in a closed room in winter, faulty gas geysers in bathrooms, generator or vehicle exhaust in an enclosed space, and smoke inhalation in house fires.
Symptoms are non-specific and are repeatedly mistaken for viral illness or food poisoning: headache, dizziness, nausea and poor concentration, progressing to confusion, syncope, seizures, arrhythmia and coma. A whole family or hostel room falling ill together is the clue.
Pulse oximetry is falsely normal and the arterial oxygen tension is normal, so the diagnosis needs carboxyhaemoglobin measured by co-oximetry on an arterial or venous sample; non-smokers normally run under 3 per cent and heavy smokers up to 10 to 15 per cent.
Treatment is oxygen: 100 per cent through a tight non-rebreathing mask or ventilator, started before any confirmation, because it shortens the half-life of carboxyhaemoglobin from about 4 to 6 hours on room air to about 60 to 90 minutes, and to 20 to 30 minutes at hyperbaric pressure.
Hyperbaric oxygen is considered for loss of consciousness at any point, neurological signs, myocardial ischaemia, severe metabolic acidosis, a carboxyhaemoglobin above about 25 per cent, and in pregnancy above about 20 per cent or with any fetal distress.
Pregnancy is treated harder and longer, because fetal haemoglobin binds carbon monoxide more avidly, fetal levels lag behind and then exceed the mother's, and the fetus can die while the mother appears to be recovering.
Cherry-red skin is a late and usually postmortem finding, not a diagnostic sign; most poisoned patients are simply pale or cyanosed.
Delayed neuropsychiatric sequelae, including memory loss, personality change, parkinsonism and incontinence, appear days to weeks after apparent recovery, so every patient needs follow-up and the family must be warned.

Digoxin toxicity

Digoxin has a narrow therapeutic index, with a usual serum range of 0.5 to 2 ng/mL and a target of 0.5 to 0.9 ng/mL in heart failure, so a small fall in renal function or in serum potassium turns a therapeutic dose into a toxic one. Toxicity is a clinical diagnosis built from gastrointestinal, visual and arrhythmic features, because a patient can be poisoned at a level inside the reported range when the potassium or magnesium is low.

Precipitants: renal impairment (digoxin is excreted unchanged by the kidney), hypokalaemia and hypomagnesaemia from loop or thiazide diuretics, hypercalcaemia, hypothyroidism, advanced age and low lean body mass.
Interacting drugs that raise the level: amiodarone, verapamil, quinidine, propafenone, macrolides, itraconazole and spironolactone; the digoxin dose is usually halved when amiodarone or verapamil is started.
Features in order: anorexia, nausea and vomiting first, then confusion in the elderly, then the classic visual disturbance of yellow-green vision with haloes and blurring.
Arrhythmias: ventricular ectopy is commonest, atrial tachycardia with atrioventricular block is the most characteristic, and bidirectional ventricular tachycardia is almost specific for digoxin. Digoxin can imitate nearly any rhythm except a rapidly conducted supraventricular tachycardia.
In acute poisoning the potassium rises because the sodium-potassium pump is blocked, and a potassium above 5 mEq/L predicts death; in chronic toxicity the potassium is usually low and must be corrected along with magnesium.
Antidote: digoxin-specific antibody fragments (digoxin immune Fab) for life-threatening arrhythmia, haemodynamic instability, hyperkalaemia after acute poisoning or a very large ingestion; each vial binds about 0.5 mg of digoxin and the response is seen within 30 to 60 minutes.
Supportive treatment: stop the digoxin, correct potassium and magnesium, atropine and temporary pacing for symptomatic bradycardia, and magnesium or lidocaine for ventricular arrhythmia. Haemodialysis does not remove digoxin, because its volume of distribution is enormous.
Electrical cardioversion is avoided unless the patient is arresting, since a digitalis-loaded myocardium can go into refractory ventricular fibrillation; if it cannot be avoided, the lowest energy is used.
Intravenous calcium for the hyperkalaemia of digoxin poisoning is traditionally avoided because of the risk of a rigid, contracted myocardium: treat the potassium with Fab, insulin with dextrose and a potassium binder instead.

Magnesium toxicity in eclampsia

Magnesium sulphate is the drug of choice for preventing and treating eclamptic convulsions, acting as a membrane stabiliser and NMDA-receptor blocker with cerebral vasodilatation, and it is superior to diazepam and phenytoin for this purpose. It is also a neuromuscular blocker, so the same drug that stops the fits will, if it accumulates, abolish the deep tendon reflexes, then depress respiration and finally stop the heart, which is why the nurse's four-hourly checks rather than the serum level are the safety system.

Pritchard regimen: 4 g of 20 per cent magnesium sulphate intravenously over 5 minutes plus 10 g of the 50 per cent solution deep intramuscularly, 5 g into each buttock, then 5 g intramuscularly every 4 hours into alternate buttocks.
Zuspan regimen: 4 g intravenously over 15 to 20 minutes as the loading dose, then a continuous infusion of 1 g per hour. Either regimen is continued for 24 hours after delivery or after the last convulsion, whichever is later.
A convulsion that recurs on treatment is managed with a further 2 g intravenously over 5 minutes, not by increasing the maintenance dose.
The therapeutic serum concentration is about 4 to 7 mEq/L (4.8 to 8.4 mg/dL), but assays are rarely available in Indian practice, so the bedside clinical checks take their place.
The order of toxicity is fixed, and that is what makes bedside monitoring safe: the knee jerk disappears first at around 10 mEq/L, respiratory depression follows at about 12 to 15 mEq/L, and cardiac arrest occurs above about 25 mEq/L.
Before every maintenance dose the nurse confirms three things: the patellar reflex is present, the respiratory rate is at least 16 per minute, and the urine output is at least 30 mL per hour or 100 mL in the last 4 hours. If any one fails, the dose is withheld and the doctor informed.
Magnesium is cleared entirely by the kidney, so oliguria or a rising creatinine means accumulation, and the maintenance dose is reduced or omitted even when the reflexes are still present.
Antidote: calcium gluconate 1 g, that is 10 mL of a 10 per cent solution, given intravenously over 10 minutes; it is drawn up and kept at the bedside with the resuscitation equipment whenever magnesium is running.
Other effects: flushing and a feeling of warmth during the injection, which is expected; neonatal hypotonia and respiratory depression when the drug is given close to delivery; and reduced uterine tone contributing to postpartum haemorrhage.

Organophosphorus poisoning

Organophosphorus compounds, the agricultural insecticides behind most poisoning deaths in rural India, phosphorylate and inactivate acetylcholinesterase, so acetylcholine accumulates at every muscarinic, nicotinic and central synapse. The patient therefore drowns in his own secretions from the muscarinic effect while the nicotinic effect paralyses the respiratory muscles: the killer is respiratory failure, and the treatment is atropine titrated to a dry, clear chest rather than to a fixed dose.

Muscarinic features (DUMBELS): Diarrhoea, Urination, Miosis, Bronchorrhoea with bronchospasm and bradycardia, Emesis, Lacrimation and Salivation with sweating. The three Bs, bronchorrhoea, bronchospasm and bradycardia, are what kill.
Nicotinic features are the opposite picture at the neuromuscular junction and sympathetic ganglia: mydriasis, tachycardia, hypertension, muscle weakness and fasciculations, with central features of confusion, seizures and coma.
Decontamination protects the staff as well as the patient: remove and bag all clothing, wash the skin and hair with soap and water, wear nitrile gloves and an apron, avoid mouth-to-mouth ventilation, and nurse the patient in a well-ventilated area.
Atropine is the life-saving drug: 2 to 5 mg intravenously in an adult (0.05 mg/kg in a child), with the dose doubled every 5 minutes until atropinisation, followed by an infusion of about 10 to 20 per cent of the total loading dose per hour.
Atropinisation is judged by a clear chest on auscultation, dry axillae, a heart rate above 80 per minute and a systolic pressure above 80 mmHg. It is not judged by the pupils, which respond last and may stay small for hours.
There is no maximum dose of atropine in this poisoning; hundreds of milligrams may be needed over a day, and the commonest fatal error is a timid fixed dose given once and then stopped.
Pralidoxime reactivates acetylcholinesterase before the enzyme ages and works mainly on the nicotinic, muscular features: 30 mg/kg intravenously over 20 to 30 minutes as loading, then 8 mg/kg per hour by infusion. It never replaces atropine.
Dangerous or contraindicated: suxamethonium, which is metabolised by the very cholinesterase that is inhibited and causes prolonged apnoea, and morphine, aminophylline, phenothiazines and furosemide before atropinisation.
The intermediate syndrome appears 24 to 96 hours after apparent recovery, with weakness of the neck flexors, proximal limbs, cranial nerves and respiratory muscles: the patient who was improving suddenly cannot lift his head off the pillow and needs ventilation.
Investigations: red cell acetylcholinesterase, which is the more accurate, or plasma pseudocholinesterase; a fall below half of normal supports the diagnosis and tracks severity, but the result must never delay atropine.

Antidotes — table

An antidote is an agent that counteracts a poison by blocking its receptor, restoring the enzyme or cofactor it destroyed, binding it directly, or supplying a competing substrate. Only a minority of poisons have one, and for most patients the airway, breathing, circulation, decontamination and supportive care are the treatment; but where an antidote exists it must be found in minutes, which is why every emergency department keeps a stocked and checked antidote list.

Paracetamol is reversed by N-acetylcysteine, which replenishes glutathione, and isoniazid overdose by pyridoxine given gram for gram with the amount of isoniazid ingested.
Opioids: naloxone 0.04 to 0.4 mg intravenously, titrated against the respiratory rate rather than the level of consciousness; its half-life is shorter than that of most opioids, so the patient is watched and the dose repeated or infused.
Benzodiazepines: flumazenil, which is rarely used because it precipitates seizures in dependent patients and in mixed overdose with tricyclic antidepressants; supportive ventilation is safer.
Anticoagulants: vitamin K1 with four-factor prothrombin complex concentrate or fresh frozen plasma for warfarin; protamine sulphate, about 1 mg for every 100 units of heparin; idarucizumab for dabigatran and andexanet alfa for the factor Xa inhibitors where they are available.
Metals: desferrioxamine for iron, calcium disodium EDTA with dimercaprol or oral succimer for lead, dimercaprol for arsenic, mercury and gold, and penicillamine for copper in Wilson disease.
Toxic alcohols: fomepizole, or ethanol where fomepizole is not available, for methanol and ethylene glycol, together with haemodialysis; folinic acid is added for methanol and thiamine with pyridoxine for ethylene glycol.
Cardiac drugs: digoxin immune Fab for digoxin; glucagon with high-dose insulin and dextrose for beta-blocker overdose; intravenous calcium with high-dose insulin euglycaemia for calcium channel blocker overdose; and sodium bicarbonate for the wide QRS of tricyclic antidepressant poisoning.
Gases and pigments: 100 per cent oxygen, with hyperbaric oxygen when indicated, for carbon monoxide; hydroxocobalamin, or sodium nitrite with sodium thiosulphate, for cyanide; and methylene blue 1 to 2 mg/kg for methaemoglobinaemia, which must not be given in G6PD deficiency.
Cholinergic and anticholinergic: atropine with pralidoxime for organophosphates; physostigmine for pure anticholinergic delirium; and neostigmine with glycopyrrolate, or sugammadex after rocuronium, to reverse neuromuscular blockade.
Indian essentials: polyvalent anti-snake venom, which covers the cobra, krait, Russell's viper and saw-scaled viper, with neostigmine and atropine as an adjunct in neurotoxic envenomation, and 20 per cent lipid emulsion for local anaesthetic systemic toxicity.
Some poisons have no antidote and are made worse by reflex treatment: in paraquat poisoning supplemental oxygen accelerates the lung injury, so oxygen is withheld unless the patient is severely hypoxic.

Emergency treatment of hypotension

Hypotension matters not as a number but as a failure of perfusion: a systolic pressure below 90 mmHg, a mean arterial pressure below 65 mmHg, or a fall of more than 40 mmHg from the patient's usual pressure, together with cold peripheries, confusion or oliguria. The emergency treatment is decided by which of the four mechanisms is at work, hypovolaemic, distributive, cardiogenic or obstructive, because the fluid that saves a septic patient will drown a patient in cardiogenic shock.

First actions that need no order: lie the patient flat and raise the legs, give oxygen, attach the monitor, insert two wide-bore cannulae, check the capillary glucose and record a full set of observations including the respiratory rate.
Hypovolaemic and septic shock: a crystalloid bolus, 30 mL/kg within the first 3 hours in sepsis, given as repeated 250 to 500 mL aliquots with reassessment after each; in haemorrhage the resuscitation fluid is blood, not crystalloid.
Noradrenaline is the first-line vasopressor for septic and most distributive shock, started at about 0.05 microgram/kg/min and titrated to a mean arterial pressure of at least 65 mmHg; it may be started through a large peripheral vein while central access is being obtained rather than delaying it.
Second-line agents: vasopressin 0.03 units per minute added to spare noradrenaline, adrenaline for refractory shock, dobutamine when the problem is pump failure with adequate filling, and hydrocortisone 200 mg a day when the vasopressor cannot be weaned.
Adrenaline 0.5 mg intramuscularly is the treatment of anaphylactic shock and comes before any fluid; neurogenic shock with bradycardia needs atropine with a vasopressor; and obstructive shock is treated mechanically, by needle decompression for tension pneumothorax, pericardiocentesis for tamponade and thrombolysis for massive pulmonary embolism.
Cardiogenic shock is the exception to fluid loading: give small 250 mL challenges at most, sit the patient up if the lungs are wet, and move early to inotropes, vasopressors and revascularisation.
Monitoring parameters with numbers: a mean arterial pressure of at least 65 mmHg, urine output of at least 0.5 mL/kg/hour, capillary refill under 3 seconds, a falling serial lactate and an improving mental state.
A passive leg raise that improves the blood pressure predicts that more fluid will help; if it does not, more fluid will only cause oedema and the answer is a vasopressor.
Vasopressor safety: an infusion pump with a dedicated line, never used for boluses or flushes, continuous or 5-minutely blood pressure monitoring, and hourly inspection of the cannula site for extravasation.

Adrenaline dose ratios

Adrenaline is supplied in ratio strengths, and the ratio is simply the weight of drug in a volume of solution: 1 in 1000 means 1 gram in 1000 mL, that is 1 mg/mL, while 1 in 10,000 means 0.1 mg/mL. Knowing which ampoule is in your hand is a life-and-death calculation, because the anaphylaxis dose is drawn from the concentrated 1 in 1000 solution for intramuscular use, while the cardiac arrest dose is given intravenously from the dilute 1 in 10,000 preparation.

The conversions: 1 in 1000 is 1 mg/mL; 1 in 10,000 is 0.1 mg/mL, that is 1 mg in 10 mL; 1 in 100,000 is 0.01 mg/mL; and 1 in 200,000 is 5 microgram/mL, the strength combined with local anaesthetics.
Anaphylaxis: 0.5 mg of 1 in 1000, that is 0.5 mL, intramuscularly into the anterolateral thigh in an adult, repeated every 5 to 15 minutes as needed; a child receives 0.01 mg/kg to a maximum of 0.5 mg, conventionally 0.3 mg between 6 and 12 years and 0.15 mg under 6 years.
Cardiac arrest: 1 mg of 1 in 10,000, that is 10 mL, intravenously or intraosseously every 3 to 5 minutes, given as early as possible in asystole and pulseless electrical activity and after the third shock in a shockable rhythm, each dose followed by a 20 mL flush and elevation of the limb.
Infusion for shock or post-arrest support: 0.05 to 0.5 microgram/kg/min, commonly 2 to 10 microgram/min in an adult, titrated to blood pressure on an infusion pump and preferably through a central line.
Neonatal resuscitation: 0.01 to 0.03 mg/kg of the 1 in 10,000 solution, that is 0.1 to 0.3 mL/kg, intravenously or through the umbilical vein, repeated every 3 to 5 minutes, and only after effective ventilation and chest compressions have been established.
Nebulised adrenaline, usually 0.5 mL/kg of the 1 in 1000 solution to a maximum of 5 mL, is used for the stridor of croup and for post-extubation laryngeal oedema, and the child must be observed for rebound obstruction over the next few hours.
With local anaesthetics, adrenaline 1 in 200,000 prolongs the block, reduces bleeding and slows systemic absorption, raising the maximum safe dose of lignocaine from about 3 mg/kg plain to about 7 mg/kg with adrenaline; the traditional teaching is to avoid adrenaline-containing solutions in the digits, nose, ear lobes and penis.
Adverse effects that decide nursing action: tachyarrhythmia, severe hypertension, angina or myocardial infarction, pulmonary oedema, and anxiety with tremor, all far more likely when the concentrated 1 in 1000 solution is given intravenously by mistake.
Storage and checking: adrenaline is light-sensitive and is kept in its carton, checked for expiry, and discarded if the solution is pink or brown or contains a precipitate, because oxidised adrenaline no longer works.

Atropine

Atropine is the prototype antimuscarinic alkaloid of Atropa belladonna: it competitively blocks acetylcholine at muscarinic receptors, removing vagal tone from the sinus and atrioventricular nodes and drying up exocrine secretions. It sits on every emergency trolley for two very different jobs, the symptomatic bradycardia of advanced life support and the muscarinic crisis of organophosphate and carbamate poisoning, and the doses for the two are not the same.

Symptomatic bradycardia in an adult: 1 mg intravenously as a bolus, repeated every 3 to 5 minutes to a maximum total of 3 mg; when it fails the next steps are transcutaneous pacing, or an infusion of dopamine 5 to 20 microgram/kg/min or adrenaline 2 to 10 microgram/min.
Organophosphate or carbamate poisoning: 2 to 5 mg intravenously in an adult, doubled every 5 minutes until the chest is clear and the axillae are dry, followed by an infusion; in this indication there is no maximum dose.
Children: 0.02 mg/kg intravenously with a minimum single dose of about 0.1 mg, and the minimum matters, because a very small dose has a central vagotonic effect and can slow the heart further, the same paradoxical bradycardia seen in adults given less than 0.5 mg.
Other uses: premedication 0.3 to 0.6 mg intramuscularly or intravenously to dry secretions and blunt vagal bradycardia, reversal of neuromuscular blockade alongside neostigmine, mydriasis and cycloplegia as eye drops, and relief of visceral colic.
Onset and duration: the intravenous cardiac effect begins within a minute and peaks at 2 to 4 minutes, the vagolytic action lasts a few hours, and the drying and pupillary effects last far longer, which is why the pupils are useless as a marker of adequate atropinisation.
Adverse effects: tachycardia, dry mouth with thirst and difficulty swallowing, blurred vision and photophobia, urinary retention, constipation, flushing, hyperthermia from suppressed sweating, which is dangerous in children and in hot weather, and confusion or delirium in the elderly.
Contraindications and cautions: narrow-angle glaucoma, benign prostatic hyperplasia with obstruction, tachyarrhythmias and thyrotoxicosis, paralytic ileus, myasthenia gravis, and hot climates in small children.
Atropine does not work, and must not delay pacing, in Mobitz type II second-degree block or complete heart block with a wide QRS escape, because the block is below the atrioventricular node; it is also ineffective in the denervated heart of a transplant recipient.
Overdose produces the classic anticholinergic toxidrome and its antidote is physostigmine given slowly with cardiac monitoring; the monitoring parameters after any atropine dose are heart rate, blood pressure, level of consciousness and urine output.

Anaphylaxis — treatment

Anaphylaxis is a severe, rapidly developing, life-threatening systemic hypersensitivity reaction, most often IgE-mediated degranulation of mast cells and basophils, producing airway swelling, bronchospasm and vasodilatory shock within minutes of exposure. It is a clinical diagnosis made at the bedside and treated with intramuscular adrenaline before any test, any antihistamine and any steroid, because the interval between onset and the first dose of adrenaline is what separates survivors from deaths.

Diagnose it when there is acute onset of illness with skin or mucosal involvement plus either respiratory compromise or hypotension, or when two or more systems are involved after a likely allergen, or when there is hypotension alone after a known allergen. Up to one case in five has no rash at all.
First-line treatment: adrenaline 0.5 mg of the 1 in 1000 solution intramuscularly into the anterolateral thigh in an adult, or 0.01 mg/kg to a maximum of 0.5 mg in a child, repeated every 5 to 15 minutes; there is no absolute contraindication to adrenaline in anaphylaxis.
Position saves lives: lie the patient flat with the legs raised, or in the left lateral position if pregnant, and sit them up only if breathing is impossible lying down. Never stand or walk an anaphylactic patient, because sudden standing has caused cardiac arrest from an empty ventricle.
Airway, breathing and circulation together: high-flow oxygen by non-rebreathing mask, a rapid crystalloid bolus of 1 to 2 litres in an adult or 20 mL/kg in a child, nebulised salbutamol for wheeze and nebulised adrenaline for stridor, with early senior anaesthetic help because the airway can close within minutes.
Second-line adjuncts that never replace adrenaline: an H1 antihistamine such as chlorphenamine, an H2 blocker, and hydrocortisone 200 mg intravenously, though steroids act too slowly for the acute event and current guidance has demoted them; glucagon 1 to 5 mg intravenously is used when a patient on beta-blockers fails to respond to adrenaline.
Refractory anaphylaxis, meaning no improvement after two intramuscular doses, needs an adrenaline infusion titrated to blood pressure, aggressive fluid resuscitation and intensive care.
Serum tryptase taken as soon as possible, again at 1 to 2 hours and once more after 24 hours as a baseline, confirms mast cell degranulation retrospectively and must never delay treatment.
Observe after recovery because of biphasic reactions: at least 6 hours after a mild reaction, and 12 to 24 hours after a severe reaction, after more than one dose of adrenaline, or when the patient lives far from medical help.
Before discharge: prescribe and demonstrate adrenaline auto-injectors where available, give a written emergency action plan, record the trigger prominently in the notes and on the identity band, and refer to an allergy service. Common triggers in Indian hospitals are beta-lactam antibiotics, NSAIDs, radiocontrast, neuromuscular blockers, latex, insect stings, and foods such as peanut, milk, egg and shellfish.

Naloxone

Naloxone is a pure competitive antagonist at mu, kappa and delta opioid receptors with no agonist activity of its own, so it displaces the opioid from the receptor and reverses respiratory depression, sedation, analgesia and miosis together. It matters at the bedside because it is the antidote a ward must be able to find in seconds, and because it wears off long before most opioids do — the patient who wakes on naloxone can stop breathing again an hour later.

Dose and route: for opioid-induced respiratory depression in a hospital patient the dose is titrated, 0.04 to 0.4 mg intravenously repeated every 2 to 3 minutes until breathing is adequate; where there is no intravenous access it is given intramuscularly, subcutaneously or intranasally, and a larger initial dose is used in an out-of-hospital overdose where the airway cannot wait.
Onset and duration: intravenously it acts within 1 to 2 minutes and intramuscularly within about 5 minutes, but the effect lasts only 30 to 90 minutes — shorter than almost every opioid it reverses and far shorter than methadone, a fentanyl patch or a modified-release preparation.
Because of that mismatch the patient is observed for hours after reversal and may need repeat boluses or a continuous infusion, which is usually started at about two-thirds of the dose that worked given each hour and then titrated; a patient who wakes after one dose is not discharged.
The governing principle is to titrate to the return of adequate ventilation and not to full wakefulness: a large bolus in a chronically dependent or postoperative patient precipitates acute withdrawal with agitation, vomiting, pain, hypertension, tachycardia, arrhythmia and, at the extreme, acute pulmonary oedema.
The adverse effects that decide nursing action are precipitated withdrawal with its cardiovascular consequences and the sudden return of severe pain in a patient who was being treated for it; naloxone has essentially no effect in someone who has not taken an opioid, which is what makes it safe to give when the diagnosis is uncertain.
Naloxone reverses opioids and nothing else: it does not touch benzodiazepines, alcohol or barbiturates, so a patient who does not respond needs the diagnosis rethought rather than more antidote — and buprenorphine, which binds tightly, may need larger doses with ventilatory support.
In the newborn, naloxone is not part of the resuscitation sequence — a depressed baby is managed with warmth, airway and ventilation — and it is not given to the baby of an opioid-dependent mother because it can precipitate seizures.
Monitoring: continuous respiratory rate and depth, sedation score, oxygen saturation, pulse and blood pressure, with the simple target of a respiratory rate above 10 to 12 per minute in a rousable patient; keep oxygen and a bag-valve-mask at the bedside and record the time of every dose so the duration of the opioid can be weighed against the duration of the antidote.
Naloxone appears on the National List of Essential Medicines and take-home naloxone is part of harm-reduction programmes; wherever an opioid infusion or a patient-controlled pump is running, naloxone and a bag-valve-mask must be immediately available on the ward.

Free today: the 10-question daily quiz · the NORCET 11 recall paper · what ₹999 unlocks — once, no auto-renewal.