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Disturbances of water, and acid-base in acute poisoning

Disturbances of water, electrolyte and acid-base metabolism may develop as a result of a direct effect of poisons on metabolic systems, or indirectly as a result of an effect of the poison on cardiorespiratory, gastrointestinal, hepatic, or renal function.

1 concentration of 8 ACID-BASE DISORDERS The can be calculated mmol/l or lower. Major adverse A low pH is referred to as aci- as follows:2 consequences of severe acidaemia daemia, and for practical purposes Anion gap = [Na+] - ([HCO -]+ include decreased cardiac output, 3 severe acidaemia may be defined as [Cl-]) a pH < 7.2 (normal range: 7.35 - decreased arterial pressure, Normal range: 8 to 16 mmol/l 7.45). reduction in the threshold for cardiac dysrhythmias, and a E.g.: Anion gap = 140 - (26 + decrease in hepatic and renal blood 106) = 8 mmol/l flow. Acidaemia causes potassium Acidaemia causes (Note: Clinicians should con- to leave cells, resulting in hyper- sult their particular laboratory’s potassium to leave kalaemia. Brain metabolism and reference ranges when assessing cells, resulting in the regulation of its volume are the anion gap, as some may impaired, resulting in progressive include the [K+] in the above hyperkalaemia. central nervous system depression formula.) Brain metabolism and coma.1 and the regulation The anion gap (unmeasured Causes of a high anion gap metabolic acidosis3,4 of its volume are anions) is a valuable calculation in the differential diagnosis of meta- • Renal failure. impaired, resulting bolic . This gap (some- • and alco- thing of a misnomer) refers to the in progressive cen- holic ketoacidosis. difference between the concentra- tral nervous system • Profuse fluid losses leading to loss tion of cations other than Na+, and of bicarbonate from the digestive depression and the concentration of anions other tract (as in severe diarrhoea). than Cl- and HCO -, in the plasma. coma. 3 Usually, the unmeasured anions • . Two types are exceed the unmeasured cations. recognised, i.e. type A, where The normal anion gap is there is evidence of impaired tis- -8 - 16 mmol/l (since the pH of the sue oxygenation, and type B, where no such evidence is Metabolic acidosis is a condition is 7.4). It is increased when apparent. Most cases of type A characterised by a low arterial pH the plasma concentration of organic lactic acidosis are caused by tis- and a reduced plasma HCO - con- anions, such as lactate or foreign 3 sue arising from circula- centration, and is usually accompa- ions, accumulates in blood. The tory failure. In poisoned nied by compensatory alveolar anion gap is increased in cases of patients type A lactic acidosis hyperventilation, resulting in a ketoacidosis, lactic acidosis, and may occur nonspecifically owing decreased PaCO . Severe metabol- other forms of acidosis in which 2 to impairment of cardiorespira- ic acidosis also implies a plasma organic anions are increased.

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tory function (e.g. as a result of Using sodium bicarbonate in severe metabolic acidosis seizures), or more specifically

where the oxygen-carrying NaHCO3 may be given undiluted as a 4.2% solution. However, some capacity of blood is impaired prefer diluting it in 5% dextrose in water or hypotonic (0.45%) saline (e.g. as in carboxyhaemoglobi- solution, depending on the clinical setting. The goal of bicarbonate naemia or methaemoglobi- therapy is to raise the blood pH to 7.3 and the plasma bicarbonate to 12 naemia). Type B lactic acidosis - 15 mmol/l. The amount necessary can be calculated using the formu- occurs with poisons that directly la: base excess x 0.3 x body weight (kg), expressed in mmol bicarbonate.

inhibit mitochondrial enzymes (One ml 8.5 % NaHCO3 = 1 mmol, or 1 ml of 4.2% = 0.5 mmol.) It is (as in cyanide poisoning). wise to give only two-thirds of the calculated amount initially, and then Therapy should focus primarily reassess the situation. To raise the plasma bicarbonate concentration on securing adequate tissue oxy- from 4 to 8 mmol/l in a 70 kg patient, one should administer 4 x 70 x genation and on identifying and 0.5, or 140 mmol of sodium bicarbonate. An average dose is 1 - 2 treating the underlying cause. mmol/kg (2 - 4 ml) of a 4.2% solution over 15 minutes. (Several formu-

Improvement of tissue oxygena- lae exist to calculate the dose of NaHCO3.) If acid-base data are not tion may require ventilatory available 1 - 2 mmol/kg body weight may be given. About 30 minutes

support, maintenance of a high must elapse after the administration of NaHCO3 before its effect can be inspired oxygen fraction, reple- judged. It is important to consider the serum level when treat- tion of , after- ing metabolic acidosis, especially in children. Metabolic acidosis load reducing agents and increases the ionised fraction of total calcium. Treatment of acidosis inotropic support. In severe aci- decreases the amount of ionised calcium, an effect which may precipi- daemia (pH < 7.2 and/or base tate tetany and/or seizures. The administration of calcium gluconate, excess > -12), the abovemen- therefore, is sometimes indicated.1,3,5,6 tioned measures may be supple- mented by cautious administra- controversial. Bicarbonate given in . Administration of 250 - 500 tion of intravenous sodium large quantities may lead to sodium mg of acetazolamide increases both bicarbonate, initially at doses of and fluid overload, to hypokalaemia, urinary pH and urine flow. Urine no more than 1 - 2 mmol/kg of and to ‘alkalosis overshoot’. Regard- pH values may increase to 7.8. body weight (see information less of whether or not sodium bicar- This procedure is, however, not below). bonate is given, the underlying cause recommended in salicylate poison- • Acute poisonings. These of the acidaemia must be identified ing, since it may worsen the central include , ethylene gly- and treated where possible (e.g. man- nervous system effects of poison- col, and salicylate poisoning. agement of ethylene glycol or ing. In tricyclic antidepressant

Both methanol and ethylene gly- methanol poisoning with fomepizole overdose, NaHCO3 is given pri- col are substrates for hepatic or ethanol, etc.). alcohol dehydrogenase and are metabolised to formic and gly- Despite the above reservations, most colic acids, respectively. experts still recommend the judicious Exposure to toluene, by sniffing use of intravenous NaHCO3 in the glue, may also cause severe management of severe metabolic aci- metabolic acidosis resulting dosis (pH < 7.2). from the stepwise metabolism of In salicylate poisoning NaHCO3 is toluene to benzoic and hippuric given to alkalinise the urine to acid. Other poisons known to enhance excretion of salicylate (ion cause metabolic acidosis include trapping) and is usually not admin- ethanol, iron, isoniazid and istered to correct the acidosis. strychnine. Although alkaline diuresis increases Management of the abovemen- the elimination of salicylates and tioned acute poisonings may phenobarbitone, it is clinically dif- require large amounts of sodium ficult to achieve a urinary pH bicarbonate to combat severe aci- above 8 with NaHCO3. In pheno- daemia. The role of sodium bicar- barbitone poisoning parenteral bonate in the management of high acetazolamide (Diamox) has been anion gap acidaemia, however, is recommended to alkalinise the

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marily to prevent the development vomiting and diarrhoea. Hypokalaemia of cardiac dysrhythmias. Plasma osmolarity Hypokalaemia (< 3 mmol/l) is often caused by excessive losses of The osmolal concentration of a K+ from the gastrointestinal tract, Respiratory acidosis is a condition solution is called osmolality when as in diarrhoea. Hypokalaemia is caused by decreased ventilation, the concentration is expressed as almost invariably present in meta- resulting in a low arterial pH, an osmoles per kilogram of water; it is bolic alkalosis. Hypokalaemia is elevated PaCO and, usually, a called osmolarity when it is 2 also a complication of theophylline compensatory increase in plasma expressed as osmoles per litre of and beta -agonist poisoning. This HCO - concentration. Causes solution.8 The major intracellular 2 3 is caused by the movement of include upper or lower airway cation is potassium, with a concen- potassium from the extracellular obstruction, status asthmaticus, tration range of 3.3 - 5.3 mmol/l. fluid into the cell. severe alveolar defects, ventilatory The major extracellular cation is restriction, central nervous system sodium, with a concentration range Intravenous potassium should be depression and neuromuscular of 135 - 147 mmol/l. Normally, given slowly, preferably through a impairment. The two last-men- the osmolarity of the extracellular central line, while monitoring the tioned entities are often complica- fluid (280 - 295 mmol/l) approxi- amplitude of the T-wave of the tions of overdoses with sedative- mates that of the intracellular fluid. ECG (10 ml of a 15% KCl solu- hypnotics (e.g. barbiturates), opi- Therefore, the plasma osmolarity is tion contains 1.5 g potassium chlo- oids, tricyclic antidepressants, bot- a convenient guide to intracellular ride, or 20 mmol of KCl). The ulism and paralytic mussel poison- osmolarity. maximum concentration of KCl in ing, to mention a few. In patients an intravenous solution should The body fluid or plasma osmolar- breathing room air a rise in PaCO2 generally not exceed 40 mmol/l. If ity can be calculated from routine will cause a fall in PaO2, which in higher concentrations are required, electrolyte measurements by the severe cases, may cause hypoxia. it should be administered in an following formula: Concomitant hypoxaemia results in ICU. type A lactic acidosis. Manage- ment is directed towards oxygena- Calculating body fluid or Correcting severe tion, respiratory support and hypokalaemia removing the underlying cause.4 2 x [Na+] + [urea] + [] in mmol/l (calculated osmolari- To correct severe hypokalaemia, adequate urine flow should be Respiratory alkalosis is a condition ty) ensured, and then potassium of hyperventilation resulting in an The osmolal gap = measured should be administered by elevated arterial pH, a low PaCO2 osmolarity - calculated osmolar- adding 30 mmol to each litre of and usually a compensatory ity. The normal range is 10 - 15 - fluid. The amount of potassium decrease in the plasma HCO3 con- mmol/l needed can also be calculated centration. Salicylate overdose is (A slightly modified formula using the following formula: known to cause respiratory alkalo- includes the plasma potassium sis, especially in adults. This is concentration: (desired K+ - measured K+) x 0.3 caused by direct stimulation of the 2 x [Na+ + K+] + [urea] + x weight in kg respiratory centre by salicylates.4,7 [glucose] For this formula a gap > 10 Hyperkalaemia WATER AND ELECTROLYTE/ mmol/l indicates unmeasured Hyperkalaemia (> 5.5 mmol/l) is OSMOLALITY osmotically active solute.) particularly common in oliguric DISTURBANCES states (acute renal failure). It is Poisons, such as digoxin and theo- also associated with rhabdomyoly- A gap greater than 15 mmol/l indi- phylline in overdose, may cause sis (often a complication of acute cates that an unmeasured osmoti- electrolyte disturbances directly by poisoning). Hyperkalaemia is also cally active solute, e.g. an alcohol, inducing shifts of a major feature of severe metabolic + is present. An elevated osmolal (especially K ) across cell mem- acidosis (due to movement of gap, together with a high anion gap branes. Poisons may also cause potassium out of the cells to the metabolic acidosis, may indicate water and electrolyte disorders extracellular fluid). Hyperkalaemia methanol or ethylene glycol poi- indirectly, for example by inducing may also be associated with an soning.9

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overdose of certain drugs that The onset of action is usually considered if the above mea- inhibit membrane ion pumps within 30 minutes. This sures fail. It could take a few (Na+/K+ATPase), an effect which should be followed by 10% hours to start a dialysis pro-

may lead to a shift of potassium dextrose/H2O at 50 ml/h to cedure. Other treatment from inside the cell to the extracel- prevent hypoglycaemia. The modalities, therefore, should lular fluid (e.g. digoxin). Other recommended paediatric dose be carried out even if dialysis poisonous substances associated of 50% dextrose/water is is anticipated. with hyperkalaemia include fluo- 1 - 2 ml (0.5 - 1.0 g)/kg • Note. The intravenous ride (opening of potassium chan- intravenously over 30 minutes administration of 10 - 20 ml nels), cyanide (depletion of adeno- (50 ml of a 50% ampoule of 10% calcium gluconate sine triphosphate), ingestion of contains 25 g dextrose). To (over 5 - 10 minutes, and potassium salts and lithium (in this solution is added 1 U of under ECG control) should cases where lithium produces renal soluble insulin per 5 gram be reserved for the manage- tubular toxicity). dextrose, or 0.1 U to 1 ml ment of the cardiodysrhythmic (0.5 g) 50% dextrose. Blood and cardioplegic effects of Management of hyperkalaemia glucose levels should be mon- hyperkalaemia. However, if according to serum levels and/or itored regularly. (Some pae- the patient initially presents ECG changes, includes the follow- diatricians use the glucose/ with cardiac dysrhythmias ing measures: insulin regimen only if other due to hyperkalaemia, the • Mild hyperkalaemia (6.0 measures fail, or in cases administration of calcium mmol/l) may respond to dimin- where potassium levels are should be a priority. ished intake (1/2 Darrow’s solu- between 9 and 10 mmol/l. Paediatricians tend to admin- tion should be avoided in chil- • Raising the pH, either with ister calcium earlier, especially

dren). Sodium bicarbonate can NaHCO3 or by hyperventila- if the serum calcium is be given if the patient is acidotic. tion, where applicable. The decreased. The recommended The acid-base status should be effectiveness of empirical paediatric dose of 10% calcium

monitored. A loop diuretic administration of NaHCO3 gluconate solution is 0.5 - 1 (furosemide 1 - 5 mg/kg) may for the treatment of life- ml/kg at a rate of 1.0 ml/min. also enhance renal potassium threatening acute hyper- Pulse rate is a useful parameter excretion. A plasma potassium kalaemia has recently been to guide the dose. Caution level above 6.0 mmol/l requires questioned. should be employed when giv- the administration of sodium • Salbutamol therapy,by ing calcium to patients on polystyrene sulfonate (Kexelate, inhalation or the intravenous digoxin, because of the risk of formerly known as Kayexelate). route. The inhalation (nebu- precipitating hypokalaemia- The dose in adults is 15 - 30 g lisation) dose in adults is 10 - related dysrhythmias. orally or 30 - 50 g by retention 20 mg (5 mg/ml solution) enema, repeated 6 hourly as over 10 minutes. In children needed, and in children 1 - 2 the recommended inhalation Hypernatraemia and g/kg/dose. The oral route is dose is 2.5 - 5 mg over 20 hyponatraemia are more effective although some minutes by nebulisation. The clinicians prefer a high-retention intravenous dose is 4 µg/kg in uncommon in acute enema. The onset of action is both adults and children. poisoning/drug usually within 30 - 60 minutes. The effect lasts for 2 - 4 overdose. • More severe cases of hyper- hours. The use of salbutamol kalaemia (potassium ≥ 7mmol/l) should only be implemented require Kexelate as well as other as adjunctive therapy to other Hypernatraemia and hypo- more aggressive and rapid-act- more traditional treatment natraemia ing measures, including: modalities. It appears to be a Hypernatraemia and hypo- • Insulin/glucose regimen. safe and reasonably effective natraemia are uncommon in acute The ratio is 1 U insulin per 2 means of treatment. It may poisoning/drug overdose. g glucose. The average dose be used as an interim mea- Hyponatraemia (< 130 mmol/l), of insulin is 5 - 10 U of regu- sure while waiting for dialysis however, has been reported to lar insulin given by intra- or other potassium-removing occur in certain cases of snakebite venous push, combined with therapies to be instituted. (e.g. berg adder and other minor 20 - 40 ml of 50% glucose. • Haemodialysis should be adder bites). The cause is not

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known, but it is probably not due The amount of sodium needed to replace the deficit can be cal- to excessive secretion of antidiuret- culated (if 130 mmol is your aim) as follows: ic hormone. Severe hyponatraemia (< 120 mmol/l) may cause convul- (130 - measured Na+) x 0.6 x weight in kg. This formula gives the sions. deficit in mmol. The administration of 40 ml normal saline per kg should raise the serum sodium by 10 mmol/l. If fluid has to be restricted, Management of hyponatraemia a 5% NaCl solution may be used (1.17 ml of a 5% NaCl solution is includes the restriction of water equal to 1 mM). Hypertonic (5%, 850 mmol/l) saline should be and the administration of sodium if administered by a central line. It is recommended to give half the cal- serum levels are < 130 mmol/l in culated dose of sodium, and then according to follow-up levels. In the cases of inappropriate ADH secre- management of acute hyponatraemia it is advisable to administer sodi- tion. um until the symptoms (convulsions) disappear and not until the serum

Hypocalcaemia (see block) sodium is normal. (NaHCO3 solution (4.2%) may also be utilised as a Hypocalcaemia is a known compli- source of sodium.) Note: As a general guideline it is recommended cation of fluoride poisoning. It is that the serum sodium not be allowed to increase by > 0.5 mmol/l/h in also associated with ethylene glycol chronic hyponatraemia (not > 2 mmol/l in 4 hours), or > 1 mmol/l/h poisoning. (The normal total (not > 4 mmol/l in 4 hours) in acute hyponatraemia. (Hyponatraemia of serum calcium is 2.05 - 2.56 more than 36 - 48 hours’ duration is considered chronic.) Serum sodi- mmol/l, the ionised calcium is 1.1 - um levels should be monitored at least 4 hourly. Inappropriate rapid 1.3 mmol/l and the -bound correction of serum sodium may produce central pontine myelinosis. calcium is 0.9 - 1.1 mmol/l.) In severe cases intravenous calcium most cases. Hypoglycaemia may also gluconate is indicated (see block). be a complication of severe paraceta- mol and Amanita phalloides poisoning The use of intravenous calci- due to liver failure. After correction SINGLE um gluconate in severe of hypoglycaemia with 50% dex- hypocalcaemia trose/H2O, a continuous infusion of SUTURE 20% glucose should be administered A little of what you fancy ... In acute symptomatic hypocal- to prevent relapse.4 caemia the intravenous dose is As drinking and abstinence 10 ml of a 10% calcium glu- References available on request. behaviour changes over time, conate solution, at a rate not some view the conventional J- exceeding 5 ml/min, repeated shaped mortality curve once, if necessary. Thereafter, (which depicts abstainers and 10 ml of 10% calcium gluconate IN A NUTSHELL heavy drinkers as having a

per litre of 5% dextrose/H2O at a Acid-base and potassium abnor- higher mortality risk than rate of 50 - 100 ml/h. The pae- malities are common in poison- those who indulge moderate- diatric dose is one-half of the ing. ly) with scepticism. When adult dose. Hypocalcaemia is Poisoning should be excluded in researchers prospectively common in children in acute cases of unexplained metabolic studied the relation by using renal failure, and calcium levels acidosis. two measurement points, they may decrease precipitously to Major adverse consequences of found that risk for consistent very low levels in rhabdomyoly- severe acidaemia include abstainers was not raised, but sis (phosphate levels may at the decreased cardiac output, for men who consistently decreased arterial blood pres- drank heavily the all-cause same time be elevated). sure, reduction in the threshold for cardiac dysrhythmias, and a mortality risk was higher. decrease in hepatic and renal Abstainers who started drink- Hypoglycaemia blood flow. ing did not improve their sur- Coma and convulsions resulting The anion gap is increased in vival rate; heavy drinkers who from hypoglycaemia occur occa- cases of ketoacidosis, lactic aci- reduced consumption did. sionally in acute poisonings. dosis, and other forms of acidosis Journal of Studies on Alcohol 2003; 64: (Normal random serum glucose is in which organic anions are 278-285 (from Minerva. BMJ 2003; 4.1 - 11.1 mmol/l.) The sulphonyl- increased, as in methanol and 326: 12 74.) ureas (oral antidiabetic agents), ethylene glycol poisoning. insulin and ethanol are implicated in

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