Role of the Intensive Care Unit in the Management of the Poisoned Patient Per Kulling and Hans Persson Swedish Poison Information Centre, Stockholm

Home , Chelation therapy, Ergotism, Salicylate poisoning

Concepts in Toxicology Review

Summary By applying a sensible toxicological approach to the general principles ofintensive care, an optimum setting for the treatment ofpoisoning is created. The intensive care unit (ICU) can perform the necessary close observation and monitoring, and thus facilitate rapid detection ofsymptoms, and the institution of early appropriate treatment. Diagnosis may be complex in poisoning and require continuous qualified interpretation of clinical and analytical data. Antidote therapy and treatment to enhance elimination ofthe poison must often be dealt with under careful supervision. The capacity ofthe ICU to counteract various toxic effects in a nonspecific way and to provide optimum symptomatic and supportive care is crucial. However, the ongoing toxic effects on the body must always be considered and allowed to guide symptomatic treatment. Thus, clinical toxicology appears to be a specialised branch of intensive care medicine.

Many patients exposed to a poison may, after is of utmost importance for a proper interpretation initial measures like clinical assessment, gastric of clinical and analytical data and an immediate lavage and administration of activated charcoal, be start for necessary therapy. In some cases the ICU managed in general wards. However, to be able to may have a laboratory of its own, offering rapid adequately treat a severely poisoned patient the fa and frequent analysis. Another important aspect of cilities of an intensive care unit (ICU) are often the ICU is that there is generally a low threshold required and the capacity of such units to provide for accepting and utilising new and advanced ther optimum conditions for diagnosis and treatment apeutic methods. All these characteristics interact has been of fundamental importance for the prog to make the ICU an ideal setting for treatment of ress of clinical toxicology. poisoning. As will become obvious from various examples In the 1950s Clemmensen claimed that careful cited below, management of acute poisoning is de symptomatic treatment was very successful in the pendent on high doctor: patient and nurse: patient management of severely poisoned patients (Clem ratios around-the-clock. Adequate observation, mensen 1954). Therapy included mainly conserv diagnosis and treatment will require a nursing staff ative support given by trained nurses. This regi with a high level of technical proficiency in such men dramatically reduced previously high mortality fields as respiratory control and cardiac monitor rates, and has been referred to as the 'Scandinavian ing. The ICU also provides advanced technical method' (Clemmensen & Nilsson 1961). equipment both for monitoring and treatment. The In many countries hospital wards are organised continuous presence of specially trained physicians according to the Clemmensen model, i.e. central- Role of the leU in Toxicology Management 376

ised wards where only poisoned patients are treated 1.2 Observation and Monitoring and where intensive care can be provided as re quired. Special intensive care units for poisoned Often the circumstances of a poisoning are un patients also exist, but most severe acute poison clear, and information about the degree or time of ings are treated in ordinary ICUs. exposure or even of the exact nature of the poison is inadequate. As no risks should be taken in these 1. The Role o/the leU in Management situations, it is necessary to keep the patient under 0/ Poisoned Patients close supervision in order to be able to promptly and effectively tackle any toxic effects that might Some aspects that characterise the need for, and emerge. the role of the ICU in observing, diagnosing and An ICU offers the facilities for early detection treating poisoned patients will be discussed. The of the onset of alarming symptoms and the rapid role of the ICU in improving the overall know initiation of appropriate therapy. As it is often a ledge of toxicology through documentation of cases question of preventing serious complications rather and scientific work will also be discussed. To bal than treating them, the careful and intensive ob ance the discussion, some negative points are also servation and monitoring of a patient at risk is a taken into account. fundamental part of the management. The main advantages of treating poisoned patients in an ICU are summarised in table 1. 1.3 Toxicological Management

1.1 Diagnosis Certain toxic effects may in themselves neces sitate treatment in an ICU, but often there is a Diagnostic procedures may be complex and are multiple toxic burden on the body that is prefer sometimes best carried out in an ICU. For exam ably dealt with in an ICU. A number of examples ple, repeated clinical evaluation, repeated collec are given be!c\v of toxicological situations where tion of specimens for analysis, x-rays, ECGs, EEGs the potential of the ICU may be most beneficial. and endoscopies may be best undertaken, inter preted and related to each other within the frame 1.3.1 Central Nervous System Disturbances work of an ICU. Additionally, the possible need Central nervous system (CNS) dysfunction is a for advanced supportive measures during the diag prominent feature of many intoxications, which nostic procedure may mean that the patient re may include depression or excitation. It is im quires transfer to an ICU. In our experience, ob portant to identify, from their history, clinical status scure cases taken immediately to the ICU will be and laboratory analyses, those patients who may diagnosed more rapidly than in the casualty or gen develop severe CNS symptoms. As severe CNS eral ward. However, essential diagnostic measures depression is generally associated with depressed must not be allowed to delay or replace any im circulation, respiration, reflex activity or body portant therapeutic steps. temperature, etc., the capacity of the ICU to pro vide nonspecific symptomatic support is of crucial Table I. Advantages of treating acute poisonings in an leu importance. This is true also for severe CNS ex citation where agitation, delirium, motor overac Rapid and accurate diagnostic procedures are available tivity and circulatory overstimulation may require Intensive observation and monitoring can be performed a complex and heavy pharmacological interven Advanced or complicated treatment measures may be tion to bring the condition under control. If the employed dose is high enough, even mildly toxic agents may Documentation of the case is facilitated induce CNS disturbances necessitating intensive observation and support. Role of the leU in Toxicology Management 377

Coma Table II. Some examples of common agents that provoke WakiQg a patient by administration of specific seizures in acute poisonings antidotes is seldom justified, at least not in an ICU. The duration of the effect of the antidote is gen Drugs erally much shorter than that of the toxic agent, Antiarrhythmics Anticholinergics and the patient will often relapse into coma several Antihistamines times. In these situations it is often better to allow eNS stimulants the patient to wake up spontaneously with opti Dextropropoxyphene mum symptomatic support. However, if the patient Disulfiram cannot be treated otherwise, reversal of the coma Isoniazid Opiates by administering specific antidotes like naloxone Orphenadrine or benzodiazepine antagonists should be consid Phenothiazines ered. In general, it may be hazardous to reverse Salicylates coma in tricyclic antidepressant poisoning by use Sympathomimetics of physostigmine, due to the likelihood of cardiac Theophylline Tri- and tetracyclic antidepressants complications (Pentei & Paterson 1980) or seiz ures. On the other hand, physostigmine may be Chemicals Camphor useful in treating severe agitation and hallucinosis 2,4-0 in the awakening period of tricyclic antidepressant Heavy metals poisoning or in other types of anticholinergic poi Lindane sonings. Organic solvents Organophosphates Strychnine Seizures Turpentine Seizure activity is an important and hazardous expression of CNS toxicity. Seizures may super vene in an already deleterious situation due to the presence of other toxic manifestations. Seizure ac tivity may be derived from a direct or indirect toxic In general, convulsions are just one manifesta influence on the CNS. One 'indirect' cause is hy tion of toxic activity in poisoning. In tricyclic anti poxia that may be induced by impaired ventila depressant or orphenadrine poisoning for example, tion, blockade of oxygen utilisation at a cellular severe myocardial dysfunction may also constitute level (cyanide, hydrogen sulphide, carbon mon a serious problem. Even transient hypoxia, slight oxide), or reduced oxygen transport capacity (car metabolic acidosis and electrolyte disturbances in bon monoxide and methaemogiobinaemia). Other duced by seizures may unfavourably affect the crit examples are hypogiycaemia, cerebral oedema and ically disturbed myocardial function. Thus, sudden metabolic disturbances such as alkalosis, acidosis onset of seizures may provoke malignant arrhyth and liver encephalopathia. Common toxins that mias and cardiac arrest. Convulsions should be re may in themselves cause seizures are listed in table garded as a serious symptom, and their treatment II. While most antiarrhythmic dy;ugs may cause must be optimal and probably include assisted convulsions, they are most commonly observed in ventilation, the indications for which are wider than poisoning with (j-blockers or quinidine-like com in seizure disorders of non-toxic origin. The treat pounds. With dextropropoxyphene (propoxy ment of seizures includes anticonvulsants such as phene) poisoning, seizures may occur in addition benzodiazepines or barbiturates, but in severe cases to respiratory depression and circulatory problems muscle relaxants must be administered to facilitate (Young 1983). Seizures may also occur in drug controlled ventilation and reduce the metabolic withdrawal states. demands. Role of the leu in Toxicology Management 378

Cerebral Oedema equate fluid replacement is of vital importance, but Cerebral oedema is a dreaded and not uncom if vascular resistance is very low, careful admin mon complication in severe poisoning due to agents istration of a vasopressor, e.g. noradrenaline (nor such as ethylene glycol, methanol, glutethimide or epinephrine) or dopamine, may be necessary. carbon monoxide. Cerebral oedema may also oc The situation may be complicated by concom cur secondary to hypoxia, hepatic encephalopathy itant myocardial depression. In these situations or seizure activity. If cerebral oedema is impend restoration of an effective plasma volume ought to ing, any tendency to hypoventilation should be be guided by central venous pressure measure avoided as hypercapnia increases cerebral blood ment, or preferably by more sophisticated intra flow and may worsen the cerebral oedema. In these vascular monitoring through a pulmonary artery situations, controlled hyperventilation should be catheter. Inotropic support with drugs including used (Gordon 1979). Restriction of fluid intake is dopamine or dobutamine may be necessary to im then also necessary. prove myocardial function and to restore adequate circulation and tissue perfusion. 1.3.2. Cardiovascular Disturbances The cardiovascular system may be affected by Cardiac Dysfunction toxins in many ways. Hypotension and shock may Severe cardiac dysfunction may occur in mas be caused by true hypovolaemia, relative hypo sive overdose of some hypnosedatives and narcot volaemia, myocardial insufficiency or a combina ics, for example, barbiturates, meprobamate and tion of factors. All types of arrhythmias may occur. opiates. At present, however, it is more often seen One of the challenges to clinical toxicology today after overdoses of cardiovascular drugs like {3- is to counteract the effects of highly potent cardio blockers, calcium channel blockers and digitalis toxic agents. An example of a problem that is yet glycosides. Poisoning from tri- and tetracyclic anti to be resolved is the reversal of cardiotoxicity in depressants is also a common cause of cardiac dys tricyclic antidepressant poisoning. function in toxicology. In these poisonings, just as in overdoses of orphenadrine, chloroquine, or other Hypovolaemia substances with membrane stabilising properties, True hypovolaemia occurs after excessive fluid severe myocardial depression may occur in com loss due to caustic skin bums, caustic lesions in the bination with bizarre ECG findings. These cases gastrointestinal tract and cytotoxic damage to the are often complicated by peripheral vasodilatation intestinal mucosa (amatoxins, arsenic). Vomiting and arrhythmias of ventricular origin. Particularly and diarrhoea may also be an expression of sys in these cases, optimum symptomatic support is temic toxicity (snake venoms, theophylline). mandatory, since even slight acidosis, electrolyte Hypovolaemia secondary to generalised toxic cap disturbances or hypoxia may aggravate the toxic illary damage with extravascular fluid loss may oc myocardial dysfunction. For example, in tricyclic cur in certain snake poisonings (Persson & Irestedt antidepressant poisoning, correction or even some 1981). Hyperventilation as in salicylate poisoning overcompensation of acidosis through intravenous and excessive sweating may also cause considera bicarbonate and mild hyperventilation may have ble fluid loss. In all these situations early and ad a dramatic effect on myocardial function (Brown equate fluid replacement with crystalloids or col et al. 1973; Hodes 1984; Kingston 1979). Infusion loids is mandatory. of a sodium load may also be of value (Dellochio Relative hypovolaemia due to peripheral pool et al. 1976; Prudhommeaux et al. 1968). Such a ing of blood is common in poisoning. Systemic re regimen may be considered in intoxications by all sistance may be reduced through vascular relaxa drugs with membrane stabilising properties, in tion, adrenergic receptor blockade, or depression of cluding dextropropoxyphene. central vasomotor tone. In these situations too, ad- Arrhythmias are also an important expression Role of the leu in Toxicology Management 379

of cardiac toxicity. They may appear as a sign of Airway Obstruction severe myocardial depression as in poisoning with If the nervous system disorder leads only to a membrane stabilising agents. In addition, direct ar blocked airway, placing the patient in the uncon rhythmogt:nic properties can be attributed to the scious position or the insertion of an oro- or naso toxin itself. Ventricular arrhythmias are typical in pharyngeal tube may solve the problem. In some tricyclic antidepressant, orphenadrine, thioridazine cases tracheal intubation is necessary although and chloral hydrate poisoning, and after exposure spontaneous breathing may still be adequate. Me to trichloroethylene and other halogenated hydro ticulous care of the airway is of importance in carbons. Life-threatening arrhythmias are also seen avoiding accumulation of secretions, atelectasis, and in aconitine poisoning (Nicolas et al. 1978), and development of pneumonia. after ingestion of the aconitine-containing plant After swallowing caustic substances airway ob monkshood, Aconitum napellus (case reports, struction may occur, especially in children below Swedish Poison Information Centre, unpublished the age of 2 years (Moulin et al. 1985). Glottic and data). epiglottic oedema may necessitate tracheal intu In digitalis poisoning, all types of arrhythmias bation until the oedema has subsided. After inges and conduction abnormalities may occur. In anti tion of caustic substances the risk of aspiration into cholinergic drug poisoning, atrial tachycardia and the bronchial tree is increased by laryngeal damage even atrial fibrillation may be seen. To combat ar impairing the protective cough reflex. rhythmias, optimum symptomatic treatment is of If early respiratory tract symptoms occur after vital importance along with appropriate antiar ingestion of paraffin (kerosene) or related products, rhythmic drug treatment. In severe bradycardia petroleum distillate aspiration pneumonia should cardiac pacing may be necessary; insertion of a be suspected and intensive observation of pulmo pacemaker while patient is asymptomatic may be nary function is crucial. Any tendency to increas wise if severe bradycardia can be expected. Specific ing or persisting hypoxia regardless of origin jus antidote treatment is now possible in digitalis poi tifies putting the patient on a ventilator with soning (Smith et al. 1982; Smolarz et al. 1985). application of positive end-expiratory pressure Rarely are the facilities of an ICU so urgently (PEEP). To avoid the development of interstitial needed as in monitoring and treating cardiovas oedema, fluid intake restriction is also important. cular dysfunction. Pulmonary Oedema PEEP may be effective in the treatment of pul 1.3.3. Respiratory Symptoms monary oedema regardless of its origin. Pulmonary oedema may supervene in a number of poisonings. Respiratory Depression and Insufficiency Cardiac failure of toxic origin is one reason, but Most substances inducing CNS depression also therapeutic volume overload should not be for cause respiratory depression. Some substances such gotten. The development of toxic pulmonary oed as the opiates, more specifically depress the res ema is also an important hazard of exposure to piratory drive. Compounds with toxic effects on irritant gases like ammonia, chlorine, nitrous ox the spinal or peripheral levels of the nervous sys ides, sulphur dioxide, phosgene, etc. In many cases, tem such as muscle relaxants, some heavy metals, this oedema is not clinically manifest for 24 to 48 botulinus toxins and certain snake venoms, may hours, and the patient must be closely observed also cause muscular weakness and respiratory in during this latent period. The value of corticoste sufficiency. Although respiratory depression and roids in the prevention and treatment of toxic pul insufficiency may be counteracted by specific anti monary damage has been the subject of consider dotes, assisted or controlled ventilation is, in most able debate, but recent observations support their cases, the only adequate therapy. use (Lorin & Kulling 1986). Role of the reu in Toxicology Management 380

In some poisonings, pulmonary capillary dam Table III. Some common substances that may induce electrolyte age may make the patient extremely vulnerable to disturbances fluid overload. Severe pulmonary oedema may oc Disturbance Substance cur in certain snake poisonings, and in salicylate and barbiturate poisoning. Pulmonary oedema is Hypokalaemia /32-Agonist bronchodilators also observed late in severe lithium poisoning. Barium Salicylates Neurogenic pulmonary oedema may occur in con Theophylline nection with massive sympathetic discharge. Tri- and tetracyclic antidepressants Hyperkalaemia /3-Blockers Adult Respiratory Distress Syndrome (ARDS) Digitalis In severe poisoning, especially after drug over Hyponatraemia Carbamazepine dose, adult respiratory distress syndrome (ARDS) Phenothiazines may complicate the clinical course. ARDS is a con Butyrophenones dition characterised by diffuse injury to the alveo Hypocalcaemia Ethylene glycol locapillary membranes of the lung. Fluid overload, Fluoride Hydrofluoric acid impaired tissue perfusion and heart failure are ex Oxalate amples of conditions that may playa role in the development of ARDS. Signs such as inadequate oxygenation in spite of increasing inspired oxygen digitalis). In barium poisoning, a pronounced and fraction, tachypnoea and pulmonary infiltrations persistent hypokalaemia will typically develop appear 12 to 24 hours after the drug overdose. Pre (Gould et al. 1973). Hypokalaemia also occurs in viously this syndrome was associated with a poor severe theophylline toxicity (Buckley et al. 1983; prognosis, but intensive care including early res Hall et al. 1984; Rose 1979) and in poisoning due piratory support with PEEP and a careful, balanced to ,8ragonist bronchodilators (Haalboom et al. therapeutic approach has considerably improved 1985). Hyperkalaemia is a severe symptom of acute thc prognosis. massive digitalis poisoning, and it has also been 1.3.4. Fluid and Electrolyte Imbalance reported in ,8-blocker overdose. As already mentioned, adequate fluid replace ment is of great importance in treating poisoned Hyponatraemia patients. This could imply proper shock therapy, Pronounced hyponatraemia has been observed but also restriction of fluids in cases of cardiac dys during treatment with certain drugs, e.g. carbam function, pulmonary damage or cerebral oedema. azepine, some phenothiazines and butyrophen To maintain an optimum water balance, the pos ones. This has been attributed to the development sible disturbances should be estimated and fluid of a 'syndrome of inappropriate antidiuretic hor therapy guided by close monitoring of urinary out mone' (SIADH) [Bartter & Schwartz 1967; Henry put, circulatory parameters and other clinical ob et al. 1977]. Severe hyponatraemia has also been servations. associated with the neuroleptic malignant syn Restoration of the electrolyte balance is always drome (see section 1.3.9). of great importance, and in certain poisonings it is vital to check the serum electrolytes repeatedly. Hypocalcaemia Some important electrolyte disturbances are sum The calcium balance may also be disturbed in marised in table III. acute poisoning, thereby provoking arrhythmias. Hypocalcaemia is a predominant sign in ethylene Hypokalaemia and Hyperkalaemia glycol, fluoride and oxalate poisonings and it is also Hypokalaemia often induces arrhythmias or in seen in theophylline poisoning. After cutaneous ex creases the arrhythmogenicity of various toxins (e.g. posure to hydrofluoric acid, severe hypocalcaemia Role of the leU in Toxicology Management 381

may develop, especially after exposure to concen possibility of poisoning. Some important agents trated solutions (Mayer & Gross 1985; Tepperman causing significant acidosis have been mentioned 1980). above. The determination of anion and osmolal gap!: provides a useful guide to the interpretation 1.3.5. Metabolic Acid-Base Disturbances of metabolic acidosis. Marked widening of both gaps in combination with acidosis strongly indi Acidosis cates poisoning with methanol or ethylene glycol Metabolic acidosis may be a typical finding of if diabetic coma can be excluded (Jacobsen et al. diagnostic import in certain poisonings (see table 1982). IV). In addition, acidosis may develop as a non Acidosis has in itself many harmful effects, such specific expression of severe systemic poisoning. as constriction of pulmonary arterioles, blockade Continual control of the acid-base balance is im of the bronchodilatory effects of catecholamines and portant, not only for assessment and correction of other drugs, induction of peripheral vasodilation, acidosis but also for following the rate of acid gen reduction of myocardial contractility, induction of eration and the treatment response. arrhythmias and hyperkalaemia (Astrup & Sever In ethylene glycol, methanol, formaldehyde and inghaus 1986). Metabolic acidosis may also aggra to some extent paraldehyde poisoning, the acidosis vate the toxic potential of many poisons; for ex is related to metabolites of the parent compounds. ample, the cardiotoxicity of tricyclic antidepressants Similarly, in certain drug poisonings (e.g. salicyl or quinidine, and the CNS toxicity of salicylates. ates, theophylline and iron), metabolic acidosis is Early correction of acidosis is always essential. a characteristic finding after massive exposure. In This must be done with caution to avoid electro these cases, the occurrence of acidosis will help in lyte disturbances or metabolic alkalosis. The need assessment of severity and choice of therapy. for buffer substitution differs considerably accord Exposure to carbon monoxide, cyanide or hy ing to the origin of the acidosis. It is of vital im drogen sulphide will cause cellular hypoxia with portance to stop the acid production as soon as subsequent lactic acidosis. In these cases the meta possible by adequate general and specific treat bolic acidosis will indicate roughly the degree of ment. exposure, and facilitate evaluation of the poisoning and choice of treatment. Hypoxia due to impaired Alkalosis tissue perfusion, hypoventilation or seizures may Metabolic alkalosis may also occur in poisoning also produce metabolic acidosis that is rather easily but it is rarely a primary toxic effect. Apart from corrected once the general clinical condition has excessive potassium loss, metabolic alkalosis may been brought under control. In addition, impaired be due to loss of hydrogen ions in states of repeated renal or hepatic function may contribute to the de vomiting. velopment of acidosis. When faced with a severe metabolic acidosis of 1.3.6 Toxic Liver Damage unknown origin, one should always consider the Signs of hepatic damage may be observed in severe systemic poisoning. Prolonged hypotension, insufficient ventilation or hypoglycaemia preced Table IV. Some typical causes of metabolic acidosis in acute ing admission to hospital, or poisoning from as poisonings phyxiating agents such as carbon monoxide, hy Ethylene glycol Paraldehyde drogen sulphide or cyanide may cause liver damage. Formaldehyde Salicylates However, hepatic injuries may also be caused di Iron Theophylline Isoniazid Toluene rectly by the action of drugs, chemicals and bio Methanol logical toxins having specific hepatoxic properties. The number of such hepatotoxins is overwhelming Role of the leU in,Toxicology Management 382

Table V. Some common agents that cause liver damage in acute liver must be tackled with extreme care. In some poisonings instances, and in some places, haemodialysis, Alcohols haemoperfusion or plasmapheresis may be in Amatoxin cluded in the therapy, especially if there is also renal Gyromitrin involvement. Iron and other metal salts Paracetamol (acetaminophen) Paraquat 1.3.7. Toxic Kidney Damage Phenylbutazone As with liver damage, kidney damage in acute Phosphorus, yellow (white) poisoning may be attributed to 2 major mechan Solvents (e.g. halogenated hydrocarbons) isms: the lesions may be directly related to a sub stance's nephrotoxic action or they may be sec ondary to systemic reactions provoked by the but only a few that are frequently observed in poison. Various types of renal injury may occur as clinical practice are presented (see table V). a reaction to drugs or chemicals, the most common Through a variety of mechanisms these agents being acute tubular necrosis which is induced exert a true cytotoxic action resulting in destruc through a variety of mechanisms. A large number tion of hepatocellular structures. It is a character of substances may be nephrotoxic; some of the more istic feature of poisonings involving a hepatotoxin commonly implicated agents are listed in table VI. that clinical and laboratory signs of liver damage Secondary renal lesions may result from circu do not appear until after an interval of 1 to 3 days latory shock and ischaemia. Renal dysfunction or more after exposure; maximum damage may not caused by haemolysis or rhabdomyolysis with sub be present until after 5 to 6 days. Exposure to a sequent precipitation of proteins in the kidneys is hepatotoxic agent therefore requires careful ob also important in clinical toxicology. A number of servation and repeated laboratory follow-up of liver drugs and chemicals may induce haemolysis. Pro function. longed coma, often before admission to ho~nit~ 1 may involve long lasting static pressure Fortunately, it is possible in some of these poi ~~ th~-~;: sonings to specifically counteract the hepatotoxic resulting in muscular ischaemia and necrosis, and action, provided therapy is started in time. The best excessive myoglobinaemia will ensue (Penn et al. example is perhaps paracetamol (acetaminophen) 1972). Rhabdomyolysis is also observed in poison poisoning, where the protective effect of N-acetyl ing caused by amphetamine or other toxins pro cysteine is well established (Prescott et al. 1979). ducing vigorous muscular activity (Artzer et aI. The use of this amino acid has also been recom 1983; Hampel et al. 1983). mended in poisoning due to carbon tetrachloride

(Ruprah et aI. 1985). Of course, chelation therapy Table VI. Some common agents that cause direct toxic kidney in heavy metal poisoning, or the use of protective damage agents after exposure to natural hepatotoxins may Aminoglycoside antibiotics also greatly influence the degree of liver damage. Arsenic However, symptomatic treatment of liver dam Carbon tetrachloride and other halogenated hydrocarbons age and subsequent failure is often the only altern Chlorate Cortinarius toxins ative. To guide the patient through such a dramatic DDT (dicophane) disturbance of vital organ functions is a delicate Ethylene glycol and other glycols task and will often require the facilities of an ICU. Mercury and other heavy metals Organophosphates Electrolyte fluid and acid-base balance must be Paracetamol (acetaminophen) maintained and coagulation disorders corrected Paraquat with a cautious and foresighted strategy. The meta Salicylates Turpentine bolic requirements and limitations of the failing Role of the lCU in Toxicology Management 383

As r'!nal damage, either truly toxic or secondary 1.3.9 Body Temperature Disturbances to systemic poisoning, often may be anticipated in the clinical situation, the objective should be to Hypothermia prevent development or progress of the injury. Hypothermia is observed in cases such as Treatment might, when appropriate, consist of spe ethanol poisoning and overdosage with some hyp cific therapeutic measures, but more often the notics, sedatives, antipsychotics and opiates. There strategy is just symptomatic. Fluids, cardiotropic is often a correlation between the severity of the or vasoactive drugs, and diuretics (mannitol in poisoning and the decrease of body temperature. hypovolaemia and 'loop' diuretics in fluid over Hypothermia is often pronounced in poisoned load) are given to restore circulation and maintain patients found in exposed environments. Therapy an adequate diuresis. In cases of haemolysis or does not differ from that of hypothermia of other rhabdomyolysis, the urine is kept alkaline through origin, and the patient should be observed closely administration of bicarbonate in order to prevent in an ICU. deposition of haemoglobin or myoglobin in the tubules (Artzer et al. 1983). Serum electrolytes and Hyperthermia the acid-base balance should be carefully moni Hyperthermia is often a more malignant expres tored and any disturbances corrected. sion of toxicity and therefore requires a more ac An aspect of particular importance is that re tive approach. It may be generated by various duced kidney function, either pre-existing or re mechanisms, and is seen in poisoning due to sali lated to the present poisoning, will add the risk of cylates, sympathomimetic drugs such as amphet a prolonged and complicated clinical course to the overall toxicity. Once renal failure is manifest it amine and caffeine, monoamine oxidase inhibitors must be treated according to general principles. Di and anticholinergics. In some of these poisonings alysis may be necessary, the purpose of which in a the hyperthermia is associated with increased mus poisoned patient is 2-fold: treatment of the renal cular activity. Administration of intravenous fluids, failure as such, and enhanced elimination of the correction of acidosis and external cooling are some toxin. In a situation where kidney damage is grad basic principles in the management of these con ually developing and the kidneys continue to be ditions, but in cases of increased muscular activity, exposed to a toxic agent, dialysis should be con muscle relaxation and controlled ventilation is often sidered on broader indications than otherwise. necessary.

1.3.8 Hypog/ycaemia Neuroleptic Malignant Syndrome Hypoglycaemia is often observed in certain poi The neuroleptic malignant syndrome is char sonings and is always a critical condition requiring acterised by hyperpyrexia, impaired consciousness, rapid treatment. As hypoglycaemia is often over muscular dystonia and elevated serum potassium looked initially, a blood glucose test is one of the and creatine phosphokinase values (Bismuth et al. most important laboratory screening tests in acute 1983). This syndrome does not usually develop un poisonings where it is also of diagnostic value. til after a considerable period of drug exposure. The Hypoglycaemia may be directly induced by the neuroleptic malignant syndrome is precipitated by poison and is seen after an overdose of insulin or treatment with various antipsychotic (neuroleptic) oral hypoglycaemics and in cases of fj-blocker, iron drugs such as the butyrophenones and phenothia or salicylate poisoning. It may also occur in intox zines; simultaneous pronounced hyponatraemia has ications with various alcohols. Secondary hypo been described (Wedzicka & Hoftbrand 1984). As glycaemia is also of clinical importance, as ob well as symptomatic measures, the recommended served in patients with hepatic disorders caused by therapy in neuroleptic malignant syndrome is a poison. administration of dantrolene sodium (Bismuth et Role of the leu in Toxicology Management 384

al. 1984; KurIan et al. 1984), as it is in malignant use of osmotic or other purgatives is also appro hyperthermia induced by certain anaesthetics. priate in a number of poisonings (Pond 1986). Forced diuresis: the use of forced diuresis is rel 1.3.10 Use o/Complicated or Hazardous evant in a few poisonings in order to enhance ur Treatment Measures inary elimination of the toxic substance. However, Although the clinical condition in itself might this measure is not free from complications such not be a reason for transferring the patient to the as hypokalaemia, pulmonary oedema, cardiac fail ICU, the treatment may include complicated or ure or cerebral oedema. As careful and frequent hazardous elements. Advanced methods for poison assessment of fluid balance is mandatory to avoid elimination is one example that is discussed in more these complications, the patient must be under close detail below. observation, preferably in an ICU. Manipulation 0/ the urinary pH: in phenobar Antidote Therapy bitone (phenobarbital), phenylbutazone, nitrofur Specific antidote therapy may justify intensive antoin, phenoxyacetate herbicides and salicylate observation and care. Treatment with anti venoms poisonings, urinary alkalinisation significantly en and antitoxins, for example, involves a risk of an hances poison elimination. This method is often aphylactic reactions that must be promptly recog recommended in combination with forced di nised and treated. Some of the heavy metal che uresis, but alkalinisation alone may be more effec lators may also cause adverse or toxic effects, and tive than the combined treatment, since it may be such therapy is therefore best carried out under difficult to keep the urine pH at a proper level when strict supervision. the urine flow is high (Prescott et al. 1982). Acid If the antidote is pharmacologically very active ification of the urine by administering ammonium and liable to produce an unwanted response along chloride is also effective in enhancing elimination with its antidotal effect, intensive care may be nec of some toxins e.g. amphetamine, phencyclidine, essary for balanced therapy. Examples are ethanol ephedrine, quinine and quinidine. However, this infusion in methanol or ethylene glycol poisoning, measure is seldom worthwhile because of the com sodium nitroprusside or glyceryl trinitrate infusion plications that may ensue: the cardiotoxicity of in ergotism, and regional intra-arterial infusion of quinine and quinidine may be increased after am calcium after cutaneous exposure to hydrofluoric monium chloride administration, and acidification acid (Velvart 1983). Another example is the use of may increase the risk of renal damage if rhabdom physostigmine for reversal of a long lasting central yolysis occurs in amphetamine, phencyclidine or anticholinergic syndrome caused by atropine or re ephedrine poisoning. lated drugs. If physostigmine has to be given re Other measures: other more sophisticated meth peatedly or through a continuous infusion, the ods for poison elimination are dialysis and haemo patient must be closely observed during the treat perfusion. However, these measures are beyond the ment. scope of this review and will not be discussed fur ther. Measures to Enhance Elimination of the Toxin 1.4 Role of the ICU in Promoting Knowledge Measures to remove a poison from the gut may in Clinical Toxicology be arduous and require intensive care. After inges tion of agents such as paraquat (Greig 1978), thal One of the characteristics of clinical toxicology lium, or large amounts of slow release drug prep is that when a new drug or chemical appears on arations, it may be justifiable to perform a thorough the market, very little or nothing at all is known gut lavage. Repeated administration of oral acti about its acute toxicity in man. Controlled clinical vated charcoal and hastening of gut passage through trials to establish toxicity data in humans are, for Role of the leu in Toxicology Management 385

obvious reasons, impossible. However, once a ever, the disadvantages should also be considered. product or a drug has been introduced a need will Firstly, certain important diagnostic aspects may arise sooner or later for information about toxicity be lost following the initial symptomatic care of and suitable treatment in case of poisoning ~ There the patient. This is particularly true for history-tak fore it is necessary to generate new documentation ing. Further, important information may not be on the basis of clinical observations and investi communicated to the ICU doctor. gations in poison centres and treatment units. Secondly, the relatively low threshold for the Partly through the intervention of the World initiation of intensive therapy in the ICU may re Health Organization and other international bod sult in unnecessary, over-aggressive and not always ies, it has now become universally recognised that innocuous, treatment. These disadvantages are poison control programmes must be established in avoidable, however, if the medical and support staff all countries in order to coordinate efforts for are aware of possible problems. countering toxic effects on man and the environ ment. In such a programme, poison centres as well 3. Conclusions as clinical toxicology units, and intensive care units in general, play a key ·role, not only through their Acute poisoning may be considered as one diagnostic and therapeutic work but also in eval among many medical emergencies, requiring im uating and documenting specific cases. mediate and extensive diagnostic and therapeutic Careful follow-up and documentation of unu intervention. The potential of modem medicine to sual or severe cases, and systematic st~dies of provide optimum conditions for this has also groups of poisonings have shed light upon a num greatly influenced the development of clinical tox ber of unsolved toxicological problems and con icology. tributed to the explosive development in clinical The diagnosis of acute poisonings may be com toxicology during recent 'years. In this way, the plex and must take into consideration the full spec properties of certain toxins have been thoroughly trum of poisoning and the need for rapid and pre evaluated and described, and new effective thera cise diagnosis in certain cases. This may require peutic measures have been developed. This work many different diagnostic measures and a contin has mainly taken place in a number of eminent uous qualified interpretation of clinical observa toxicology treatment units, but also in general in tions and laboratory data. Specific therapy, e.g. en tensive care units. In order to promote the overall hancement of poison elimination or specific knowledge in clinical toxicology, it must be stressed antidote therapy, may be complicated and even that in this context, any ICU faced with an unusual hazardous, and it may therefore require the facil or severe poisoning should be encouraged to docu ities of an ICU. However, the most fundamental ment all possible aspects of the case, both clinical contribution of the ICU in the management of poi and analytical. In general, poison centres are very soning is the capacity to provide optimum condi anxious to support such activities and to furnish tions for observation, monitoring and sympto information and analytical facilities as needed. No matic treatment. The diagnostic and therapeutic doubt great benefit should come from increased power of the ICU coupled with a sensible aware collaboration within countries and across national ness of specific toxicological problems, will create borders. The ultimate purpose is to combat the ef an ideal environment for the management of poi fects of toxins on man in a more effective way. soning. In order to evaluate risks, define symptomatol 2. Disadvantages of leu treatment ogy and elaborate new effective treatment meth ods, it is necessary to carefully document unusual Evidence supporting the role of an ICU in the or severe cases and to systematically study various treatment of poisonings is readily available. How- groups of poisonings. As such investigations are Role of the ICU in Toxicology Management 386

generally linked to clinical situations, the role of Jacobsen D,'Bredesen JE, Eide I, Oestborg J. Anion and osmolal gaps in the diagnosis of methanol and ethylene glycol poison the leu as a generator of toxicological data is also ing. Acta Medica Scandinavica 212: 17-20, 1982 worthy of emphasis. Kingston ME. Hyperventilation in tricyclic antidepressant poi soning. Critical Care Medicine 7: 550-552, 1979 Kurian R, Hamill R, Shoulson I. Neuroleptic malignant syn Acknowledgement drome. Clinical Neuropharmacology 7: 109-120, 1984 Lorin H, Kulling P. The Bhopal tragedy: what has Swedish dis· aster medicine planning learnt from it? Journal of Emergency We are grateful to Associate Professor Dr Jan Eklund, Medicine 3: in press, 1986 Head of the ICU at the Karolinska Hospital, Stockholm, Mayer TG, Gross PL. Fatal systemic fluorisis due to hydrofluoric acid burns. Annals of Emergency Medicine 14: 149-153, 1985 for his valuable and constructive criticism. 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Sodium bicarbonate and hyperventilation in treating an mfant with severe overdose of tricyclic antidepressant. Brit Authors' address: Dr Per Kulling, Swedish Poison Information ish Medical Journal 288: 1800-180 I, 1984 Centre, Box 60 500, 104 01 Stockholm (Sweden).