CLINICAL TOXICOLOGY 8(4), pp. 475-482 (1975)
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LETTER TO THE EDITOR
Guide to Management of Drug Overdose
T O Consulting Faculty of the Institute of Clinical Toxicology FROM: E r i c G. Comstock, M.D. Institute of Clinical Toxicology P.O. Box 2565 Houston, Texas 77001
Discussion on General Treatment for Drug Overdose Enclosed is a copy of a proposed manuscript to be included in the inside back cover of the 1975 Physician's Desk Reference. Minor alteration can still be made. Your suggestions on the discussion will help to stengthen the text and help avoid inaccuracies. Its publication in 600,000 copies of the PDR is, I believe, a major achievement for Clinical Toxicology. GUIDE T O MANAGEMENT O F DRUG OVERDOSE Physician's Desk Reference 29th Edition 1975. Published by: Medical Economics. Prepared by Institute of Clinical Toxicology E r i c G. Comstock, M.D., Director.
475
476
LETTER TO THE EDITOR
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INTRODUCTION The following discussion is designed for use in adult patients. In the pediatric age group, the general principles apply, but volumes of fluid o r suggested medication must be adjusted to be appropriate for body size. Symptomatic and supportive care is the approach to drug overdose upon which primary reliance should be placed. All other approaches to treatment are secondary to the support of vital function. Procedures directed toward the offending substance, such as the performance of gastric lavage or the administration of specific pharmacologic antagonist, should be undertaken only after adequate vital function has been assured. Procedures to facilitate excretion of toxic substances, such as peritoneal o r extracorporeal lavage and forced diuresis are required infrequently, and never should be relied upon as the primary approach to treatment. For sedative, hypnotic, and tranquilizer drugs, alone or in combination, supportive care is sufficient as outlined in the following discussion. I N I T I A L ASSESSMENT The initial assessment of a drug overdosed patient should determine whether the patient is asymptomatic or symptomatic. If the patient is symptomatic, determine the adequacy of respiration and cardiac function and note reflex activity, such as pupilary, corneal, gag and deep tendon. If vital function is compromised, or consciousness is impaired, proceed immediately to supportive measures. T H E ASYMPTOMATIC P A T I E N T The drug overdosed patient may be asymptomatic because he has not ingested a sufficient dose of the drugs, o r because a sufficient quantity of the drugs has not been absorbed to produce symptoms. After the ingestion of a life threatening quantity of drugs, symptoms may be delayed as long as six hours, although ordinarily symptoms are manifested within thirty (30)minutes to two (2) hours. Ingestion of alcohol simultaneously with drugs may result in symptoms as early as ten to fifteen minutes with compromise of vital function within thirty minutes. Vomiting should be induced only during the asymptomatic interval. If significant central nervous system depression intervenes between the administration of emetic and the occur-
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477
rence of vomiting, then the airway should be protected by insertion of a cuffed endotracheal tube. The delay between the administration of an emetic and the occurrence of emesis can be avoided by the use of apomorphine. Fluids must be forced orally to obtain satisfactory results from any effort to induce vomiting. An alternate approach to the asymptomatic patient alleged to have ingested drugs, is the administration by mouth of a slurry of activated charcoal containing no less than 100 grams of activated charcoal powder (USP) in water. Gastric lavage with a large caliber tube (34 French) may be performed in the asymptomatic patient o r in the patient whose consciousness is impaired but whose reflexes are intact. Any patient whose consciousness is impaired to the point where a cuffed endotracheal tube will be tolerated should be intubated prior to the performance of gastric lavage. THE SYMPTOMATIC PATIENT If the patient is symptomatic all treatment procedures directed toward the toxic substance are secondary to appraisal and support of the vital function. If the patient is in deep coma, attention to respiratory support and cardiac function should proceed immediately and simultaneously.
RESPIRATORY SUPPORT Examine the mouth. Remove all foreign material including dentures. Position the head so that respiration is not sonorous and so that regurgitated stomach contents are not readily aspirated. If respiration is not present, provide mechanical ventilation by mouth-to-mouth, ambu bag, o r positive pressure respirator until the patient is adequately oxygenated. Insert an oropharyngeal airway and suction excess excretions while preparing to insert an endotracheal tube. A cuffed endotracheal tube should be inserted and the cuff inflated. Bronchial suction should be administered to clear mucus and foreign material from the major bronchi. Determine that the chest is being inflated symmetrically and that breath sounds are audible bilaterally. After the acute emergency, determine placement of the endotracheal tube by x-ray. Monitor adequacy of ventilation using arterial blood gases.
478
LETTER TO THE EDlTOR
Clinical Toxicology Downloaded from informahealthcare.com by University of Auckland on 12/06/14 For personal use only.
IV A C C E S S AND C A R D I A C F U N C T I O N While one member of the treatment team is assuring adequate ventilation, a second member of the team should be assuring adequate IV access by insertion of an 18 guage venous catheter and initiation of IV fluid administration, such as Ringers Lactate, a t a maintenance rate in adults of 150 ml. per hour. Since hypotension from sedative drug intoxication results from relative hypovolemia complicated frequently by dehydration, the rate of intravenous infusion should be increased to 10-20 cc per minute if the systolic pressure is under 80 mm of mercury. When the systolic pressure returns to 80 mm, the rate of infusion should be reduced to 2-3 cc per minute. A central venous pressure catheter and monitoring of central venous pressure is required if the continuous high rate infusion reaches one (1)liter o r if the positive fluid balance exceeds two ( 2 ) liters during the first two hours. Intermittent monitoring of central venous pressure should continue throughout the period of intensive supportive care. A baseline electrocardiogram should be obtained as soon as procedures for support of vital function have been implemented. A n abnormal electrocardiogram should result in reduction in the rate of IV infusion to baseline of 2 ml per minute until the cardiac abnormality has been evaluated. The appearance of conduction defects should lead to suspicion of drugs with direct cardiac affects, such as the tricyclic antidepressents. In uncomplicated sedative drug overdose, the central venous pressure will be under ten centimeters of water and will not change appreciably with high volume fluid infusion. If the central venous pressure increases abruptly in excess of five centimeters of water, o r if the C V P exceeds 16 centimeters of water, high rate fluid infusion should be stopped pending evaluation of cardiac status. Adequate tissue perfusion is obtained with a systolic pressure in the range of 80 to 100 milliliters of mercury. A systolic pressure higher than this is required only in the patient with preexisting hypertension. The formation of urine is an indication that tissue perfusion is adequate.
URINARY C A T H E T E R I Z A T I O N An in-dwelling urinary catheter should be inserted early in the course of treatment of any unconscious drug overdose patient. Upon insertion of the catheter, the volume of residual urine should be measured and the specimen should be saved separately for urinalysis including specific gravity, labeled for drug analysis, and sent
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479
to the laboratory to be retained for 24 hours. The specific gravity of the initial urine will help identify patients who are severely dehydrated at the time of admission and influence the amount of positive fluid balance which should be tolerated during the initial few hours of treatment. Recording of urine output hourly is necessary to maintain fluid balance records. Continuing urine formation is a guide to the adequacy of tissue perfusion. Abrupt cessation of urine output most frequently is due to an obstructed catheter, but deserves immediate appraisal. Anuria for a period in excess of one hour should lead to reduction of high rate intravascular volume infusion until cardiac and renal status has been reappraised. Failure to achieve adequate urinary output after initial emptying of the bladder may reflect uncompensated dehydration and relative hypovolemia, each of which must be corrected before balanced fluid intake and output plus insensible loss can be achieved. The immediate or automatic use of diuretics a t this stage only aggravates the basic defect and may result in intractable hypotension. Addition of vasopresser drugs a t this stage may precipitate renal failure. Relatively mobile electrolite solutions as transient volume expanders a r e preferred to whole blood or plasma to avoid congestive failure when normal vascular tone is re- established. A positive fluid balance of 2 to 4 liters may be required before fluid intake and output are in equilibrium. A s vascular tone returns, urine output may increase abruptly, exceeding one liter per hour. Profound diuresis may preceed recurrence of deep tendon reflexes and heralds reduction in CNS depression. GASTRIC LAVAGE Gastric lavage should be performed only after vital function has been determined to be adequate o r procedures for support of vital function have been implemented. Gastric lavage should be undertaken only after a cuffed endotracheal tube is protecting the airway. If corrosive substances are thought to have been ingested, lavage should not be performed until examination demonstrates there is no destruction of the mucous membranes of the mouth o r of the esophagus as determined by esophagoscopy. Gastric lavage should be performed if the ingestion of drugs is estimated to have been within the preceding six hours. If there are no audible bowel sounds, gastric lavage should be performed regardless of the time lapse between ingestion and treatment. A 34 French lavage tube should be used. Smaller tubes do not permit sufficiently rapid fluid flow to remove particulate material. Gastric contents should be aspirated prior to
Clinical Toxicology Downloaded from informahealthcare.com by University of Auckland on 12/06/14 For personal use only.
480
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lavage and saved in the event subsequent laboratory analysis is required. In an adult, lavage should be performed in cycles of 300 to 500 milliliters of fluid instilled over one to two minutes, left in place for about one minute, and drained by gravity over a period of approximately three to four minutes. If these time intervals cannot be accomplished, then the lavage system is defective. The total fluid volume to be used in lavage should be three liters beyond that volume required to obtain a clear return. Lavage may be performed with tap water or a normal saline solution. Other lavage fluids such as dilute potassium permanganate, copper sulfate, bicarbonate, tannic acid, and castor oil are occasionally recommended, but accidental aspiration of these substances may result in pneumonic processes of greater hazard than the primary substance. Powdered activated charcoal is an effective substitute and is less hazardous with aspiration than plain gastric secretions. A C T I V A T E D CHARCOAL Powdered activated charcoal effectively adsorbs sedative and tranquilizer drugs and a vast majority of other drugs, thereby limiting their bio-availability. Upon the completion of lavage, 100 grams of dry powdered activated charcoal (USP) suspended in six ounces of water to form a slurry easily passed through the lavage tube should be instilled and left in place in the stomach. The activated charcoal forms an effective barrier between any remaining particulate material and the gastrointestinal mucosa. Drugs adsorbed on activated charcoal a r e not desorbed to any practical extent in the lower intestinal tract. When an enteroenteric circulation of the active drug exists, excess activated charcoal in the intestine effectively prevents reabsorption thereby facilitating excretion. This appears effective with the tricyclic antidepressants and the cardiac glycosides. Activated charcoal is not effective with cyanide or small electrolytes such as sodium, potassium, chloride, o r mineral acids or bases. S P E C I F I C ANTIDOTES
Specific antidotal substances effective in the treatment of drug overdose a r e few. They should be used only with specific indications and never should be used prophylacticly or in quantities sufficient to return the comatose patient to consciousness. They should be used only to improve adequacy of vital function and never be relied
LETTER TO THE EDlTOR
481
Clinical Toxicology Downloaded from informahealthcare.com by University of Auckland on 12/06/14 For personal use only.
upon at the exclusion of supportive care. When specific antidotes are used, special attention must be given to duration of action of the antidote as compared with the duration of action of the primary drug. Release of a patient after administration of a relatively short-acting antidote may result in serious compromise of clinical status after the patient has been released from medical care. AVOID UNNECESSARY DRUGS Whenever possible, support of vital function should be by mechanical rather than by chemical means. Inadequate respiration should be corrected by using a positive pressure respirator rather than by use of respiratory stimulant drugs. Central nervous system depression and coma should be treated by the supportive means described above and should not be treated by central nervous system stimulant drugs. Shortening of coma with CNS stimulant drugs may result in hyperpyrexia and convulsions which otherwise might be avoided. Hypotension resulting from sedative or tranquilizer drug overdose is due to relative hypovolemia properly corrected by increasing the intravascular volume. Vasopressor drugs a r e not helpful and should be avoided. Body temperature outside of the normal range should be controlled by heat exchangers which warm o r cool the body mechanically. Antipyretic drugs should be avoided. Antipyretic drugs in overdose cause hyperpyrexia. Forced diuresis is not conservative supportive care. Forced diuresis with alkalinization of the urine is an effective treatment for increasing the excretion of salicylates. Alkaline diuresis also is effective in removing phenobarbital and barbitol, but only rarely is it an essential part of treatment of overdose due to these drugs. The risk benefit ratio of forced diuresis in the treatment of other drugs does not favor its use. Diuretic drugs should not be a routine measure in the treatment of drug overdose. Diuretics should be reserved for use in substances clearly excreted in the urine in active form or for treatment of overhydration and cerebral edema. CONTINUING CARE
Coma from sedative drug intoxication may persist for many days. Total apnea for five days and an isoelectric electoencephalogram for intervals up to 36 hours have been recorded with drug overdose patients who have survived without apparent neurologic sequelae. Continuing care should be provided in a medical intensive care unit with
Clinical Toxicology Downloaded from informahealthcare.com by University of Auckland on 12/06/14 For personal use only.
482
LETTER TO THE EDITOR
monitoring of temperature, blood pressure, pulse, respiratory rate, tidal volume, electrocardiogram, central venous pressure, fluid balance, electrolytes, and arterial blood gases with appropriate compensatory treatment for abnormalities. Intensive respiratory care should include frequent tracheal suction, frequent repositioning, and daily chest x-rays. Endotracheal tubes should be changed under supervision of an anesthesiologist. Tracheostomy should be performed only for surgical indications. Carefully attentive continuous nursing care is essential. COMPLICATIONS Aspiration pneumonia and subsequent infection is the most commonly occurring complication of coma secondary to drug overdose. Treatment consists of vigorous tracheal aspiration, periodic hyper inflation of lung, and antibiotic coverage. Rarely occurring are tension pneumothorax and renal failure of the crush syndrome type. Interstitial edema, including scleredema, is common in profound coma and usually represents increased capillary permeability rather than over hydration. Parenteral steroids may be helpful in this situation. Occasionally, interstitial edema is so severe as to compromise venous return and to require fasciotomies to provide venous drainage. Always be mindful that the patient may have sustained traumatic injury especially to the head, so be watchful for lateralizing neurologic signs. T O X I C O L O G I C ANALYSIS Any ingested material, initial gastric aspirate, and the first catheterized urine specimen all should be saved and labeled for laboratory examination with instructions to hold at least twentyfour (24) hours prior to discarding. Analysis of these fluids for drugs occasionally will change fundamental approach to treatment. Qualitative analysis provides confirmation of the clinical determination of etiology. Frequently multiple drugs are involved. Interpretation of quantitative findings is extremely difficult and usually is helpful only to follow the clearance of substances from the body. Previous drug use results in tolerance which prevents meaningful interpretation of absolute concentrations. Instructions for management of specific drugs identified should be consulted once symptomatic and supportive care is underway.
Clinical Toxicology Downloaded from informahealthcare.com by University of Auckland on 12/06/14 For personal use only.
LETTER TO THE EDITOR
Guide to Management of Drug Overdose
T O Consulting Faculty of the Institute of Clinical Toxicology FROM: E r i c G. Comstock, M.D. Institute of Clinical Toxicology P.O. Box 2565 Houston, Texas 77001
Discussion on General Treatment for Drug Overdose Enclosed is a copy of a proposed manuscript to be included in the inside back cover of the 1975 Physician's Desk Reference. Minor alteration can still be made. Your suggestions on the discussion will help to stengthen the text and help avoid inaccuracies. Its publication in 600,000 copies of the PDR is, I believe, a major achievement for Clinical Toxicology. GUIDE T O MANAGEMENT O F DRUG OVERDOSE Physician's Desk Reference 29th Edition 1975. Published by: Medical Economics. Prepared by Institute of Clinical Toxicology E r i c G. Comstock, M.D., Director.
475
476
LETTER TO THE EDITOR
Clinical Toxicology Downloaded from informahealthcare.com by University of Auckland on 12/06/14 For personal use only.
INTRODUCTION The following discussion is designed for use in adult patients. In the pediatric age group, the general principles apply, but volumes of fluid o r suggested medication must be adjusted to be appropriate for body size. Symptomatic and supportive care is the approach to drug overdose upon which primary reliance should be placed. All other approaches to treatment are secondary to the support of vital function. Procedures directed toward the offending substance, such as the performance of gastric lavage or the administration of specific pharmacologic antagonist, should be undertaken only after adequate vital function has been assured. Procedures to facilitate excretion of toxic substances, such as peritoneal o r extracorporeal lavage and forced diuresis are required infrequently, and never should be relied upon as the primary approach to treatment. For sedative, hypnotic, and tranquilizer drugs, alone or in combination, supportive care is sufficient as outlined in the following discussion. I N I T I A L ASSESSMENT The initial assessment of a drug overdosed patient should determine whether the patient is asymptomatic or symptomatic. If the patient is symptomatic, determine the adequacy of respiration and cardiac function and note reflex activity, such as pupilary, corneal, gag and deep tendon. If vital function is compromised, or consciousness is impaired, proceed immediately to supportive measures. T H E ASYMPTOMATIC P A T I E N T The drug overdosed patient may be asymptomatic because he has not ingested a sufficient dose of the drugs, o r because a sufficient quantity of the drugs has not been absorbed to produce symptoms. After the ingestion of a life threatening quantity of drugs, symptoms may be delayed as long as six hours, although ordinarily symptoms are manifested within thirty (30)minutes to two (2) hours. Ingestion of alcohol simultaneously with drugs may result in symptoms as early as ten to fifteen minutes with compromise of vital function within thirty minutes. Vomiting should be induced only during the asymptomatic interval. If significant central nervous system depression intervenes between the administration of emetic and the occur-
Clinical Toxicology Downloaded from informahealthcare.com by University of Auckland on 12/06/14 For personal use only.
LETTER TO THE EDITOR
477
rence of vomiting, then the airway should be protected by insertion of a cuffed endotracheal tube. The delay between the administration of an emetic and the occurrence of emesis can be avoided by the use of apomorphine. Fluids must be forced orally to obtain satisfactory results from any effort to induce vomiting. An alternate approach to the asymptomatic patient alleged to have ingested drugs, is the administration by mouth of a slurry of activated charcoal containing no less than 100 grams of activated charcoal powder (USP) in water. Gastric lavage with a large caliber tube (34 French) may be performed in the asymptomatic patient o r in the patient whose consciousness is impaired but whose reflexes are intact. Any patient whose consciousness is impaired to the point where a cuffed endotracheal tube will be tolerated should be intubated prior to the performance of gastric lavage. THE SYMPTOMATIC PATIENT If the patient is symptomatic all treatment procedures directed toward the toxic substance are secondary to appraisal and support of the vital function. If the patient is in deep coma, attention to respiratory support and cardiac function should proceed immediately and simultaneously.
RESPIRATORY SUPPORT Examine the mouth. Remove all foreign material including dentures. Position the head so that respiration is not sonorous and so that regurgitated stomach contents are not readily aspirated. If respiration is not present, provide mechanical ventilation by mouth-to-mouth, ambu bag, o r positive pressure respirator until the patient is adequately oxygenated. Insert an oropharyngeal airway and suction excess excretions while preparing to insert an endotracheal tube. A cuffed endotracheal tube should be inserted and the cuff inflated. Bronchial suction should be administered to clear mucus and foreign material from the major bronchi. Determine that the chest is being inflated symmetrically and that breath sounds are audible bilaterally. After the acute emergency, determine placement of the endotracheal tube by x-ray. Monitor adequacy of ventilation using arterial blood gases.
478
LETTER TO THE EDlTOR
Clinical Toxicology Downloaded from informahealthcare.com by University of Auckland on 12/06/14 For personal use only.
IV A C C E S S AND C A R D I A C F U N C T I O N While one member of the treatment team is assuring adequate ventilation, a second member of the team should be assuring adequate IV access by insertion of an 18 guage venous catheter and initiation of IV fluid administration, such as Ringers Lactate, a t a maintenance rate in adults of 150 ml. per hour. Since hypotension from sedative drug intoxication results from relative hypovolemia complicated frequently by dehydration, the rate of intravenous infusion should be increased to 10-20 cc per minute if the systolic pressure is under 80 mm of mercury. When the systolic pressure returns to 80 mm, the rate of infusion should be reduced to 2-3 cc per minute. A central venous pressure catheter and monitoring of central venous pressure is required if the continuous high rate infusion reaches one (1)liter o r if the positive fluid balance exceeds two ( 2 ) liters during the first two hours. Intermittent monitoring of central venous pressure should continue throughout the period of intensive supportive care. A baseline electrocardiogram should be obtained as soon as procedures for support of vital function have been implemented. A n abnormal electrocardiogram should result in reduction in the rate of IV infusion to baseline of 2 ml per minute until the cardiac abnormality has been evaluated. The appearance of conduction defects should lead to suspicion of drugs with direct cardiac affects, such as the tricyclic antidepressents. In uncomplicated sedative drug overdose, the central venous pressure will be under ten centimeters of water and will not change appreciably with high volume fluid infusion. If the central venous pressure increases abruptly in excess of five centimeters of water, o r if the C V P exceeds 16 centimeters of water, high rate fluid infusion should be stopped pending evaluation of cardiac status. Adequate tissue perfusion is obtained with a systolic pressure in the range of 80 to 100 milliliters of mercury. A systolic pressure higher than this is required only in the patient with preexisting hypertension. The formation of urine is an indication that tissue perfusion is adequate.
URINARY C A T H E T E R I Z A T I O N An in-dwelling urinary catheter should be inserted early in the course of treatment of any unconscious drug overdose patient. Upon insertion of the catheter, the volume of residual urine should be measured and the specimen should be saved separately for urinalysis including specific gravity, labeled for drug analysis, and sent
Clinical Toxicology Downloaded from informahealthcare.com by University of Auckland on 12/06/14 For personal use only.
LETTER TO THE EDITOR
479
to the laboratory to be retained for 24 hours. The specific gravity of the initial urine will help identify patients who are severely dehydrated at the time of admission and influence the amount of positive fluid balance which should be tolerated during the initial few hours of treatment. Recording of urine output hourly is necessary to maintain fluid balance records. Continuing urine formation is a guide to the adequacy of tissue perfusion. Abrupt cessation of urine output most frequently is due to an obstructed catheter, but deserves immediate appraisal. Anuria for a period in excess of one hour should lead to reduction of high rate intravascular volume infusion until cardiac and renal status has been reappraised. Failure to achieve adequate urinary output after initial emptying of the bladder may reflect uncompensated dehydration and relative hypovolemia, each of which must be corrected before balanced fluid intake and output plus insensible loss can be achieved. The immediate or automatic use of diuretics a t this stage only aggravates the basic defect and may result in intractable hypotension. Addition of vasopresser drugs a t this stage may precipitate renal failure. Relatively mobile electrolite solutions as transient volume expanders a r e preferred to whole blood or plasma to avoid congestive failure when normal vascular tone is re- established. A positive fluid balance of 2 to 4 liters may be required before fluid intake and output are in equilibrium. A s vascular tone returns, urine output may increase abruptly, exceeding one liter per hour. Profound diuresis may preceed recurrence of deep tendon reflexes and heralds reduction in CNS depression. GASTRIC LAVAGE Gastric lavage should be performed only after vital function has been determined to be adequate o r procedures for support of vital function have been implemented. Gastric lavage should be undertaken only after a cuffed endotracheal tube is protecting the airway. If corrosive substances are thought to have been ingested, lavage should not be performed until examination demonstrates there is no destruction of the mucous membranes of the mouth o r of the esophagus as determined by esophagoscopy. Gastric lavage should be performed if the ingestion of drugs is estimated to have been within the preceding six hours. If there are no audible bowel sounds, gastric lavage should be performed regardless of the time lapse between ingestion and treatment. A 34 French lavage tube should be used. Smaller tubes do not permit sufficiently rapid fluid flow to remove particulate material. Gastric contents should be aspirated prior to
Clinical Toxicology Downloaded from informahealthcare.com by University of Auckland on 12/06/14 For personal use only.
480
LETTER TO THE EDITOR
lavage and saved in the event subsequent laboratory analysis is required. In an adult, lavage should be performed in cycles of 300 to 500 milliliters of fluid instilled over one to two minutes, left in place for about one minute, and drained by gravity over a period of approximately three to four minutes. If these time intervals cannot be accomplished, then the lavage system is defective. The total fluid volume to be used in lavage should be three liters beyond that volume required to obtain a clear return. Lavage may be performed with tap water or a normal saline solution. Other lavage fluids such as dilute potassium permanganate, copper sulfate, bicarbonate, tannic acid, and castor oil are occasionally recommended, but accidental aspiration of these substances may result in pneumonic processes of greater hazard than the primary substance. Powdered activated charcoal is an effective substitute and is less hazardous with aspiration than plain gastric secretions. A C T I V A T E D CHARCOAL Powdered activated charcoal effectively adsorbs sedative and tranquilizer drugs and a vast majority of other drugs, thereby limiting their bio-availability. Upon the completion of lavage, 100 grams of dry powdered activated charcoal (USP) suspended in six ounces of water to form a slurry easily passed through the lavage tube should be instilled and left in place in the stomach. The activated charcoal forms an effective barrier between any remaining particulate material and the gastrointestinal mucosa. Drugs adsorbed on activated charcoal a r e not desorbed to any practical extent in the lower intestinal tract. When an enteroenteric circulation of the active drug exists, excess activated charcoal in the intestine effectively prevents reabsorption thereby facilitating excretion. This appears effective with the tricyclic antidepressants and the cardiac glycosides. Activated charcoal is not effective with cyanide or small electrolytes such as sodium, potassium, chloride, o r mineral acids or bases. S P E C I F I C ANTIDOTES
Specific antidotal substances effective in the treatment of drug overdose a r e few. They should be used only with specific indications and never should be used prophylacticly or in quantities sufficient to return the comatose patient to consciousness. They should be used only to improve adequacy of vital function and never be relied
LETTER TO THE EDlTOR
481
Clinical Toxicology Downloaded from informahealthcare.com by University of Auckland on 12/06/14 For personal use only.
upon at the exclusion of supportive care. When specific antidotes are used, special attention must be given to duration of action of the antidote as compared with the duration of action of the primary drug. Release of a patient after administration of a relatively short-acting antidote may result in serious compromise of clinical status after the patient has been released from medical care. AVOID UNNECESSARY DRUGS Whenever possible, support of vital function should be by mechanical rather than by chemical means. Inadequate respiration should be corrected by using a positive pressure respirator rather than by use of respiratory stimulant drugs. Central nervous system depression and coma should be treated by the supportive means described above and should not be treated by central nervous system stimulant drugs. Shortening of coma with CNS stimulant drugs may result in hyperpyrexia and convulsions which otherwise might be avoided. Hypotension resulting from sedative or tranquilizer drug overdose is due to relative hypovolemia properly corrected by increasing the intravascular volume. Vasopressor drugs a r e not helpful and should be avoided. Body temperature outside of the normal range should be controlled by heat exchangers which warm o r cool the body mechanically. Antipyretic drugs should be avoided. Antipyretic drugs in overdose cause hyperpyrexia. Forced diuresis is not conservative supportive care. Forced diuresis with alkalinization of the urine is an effective treatment for increasing the excretion of salicylates. Alkaline diuresis also is effective in removing phenobarbital and barbitol, but only rarely is it an essential part of treatment of overdose due to these drugs. The risk benefit ratio of forced diuresis in the treatment of other drugs does not favor its use. Diuretic drugs should not be a routine measure in the treatment of drug overdose. Diuretics should be reserved for use in substances clearly excreted in the urine in active form or for treatment of overhydration and cerebral edema. CONTINUING CARE
Coma from sedative drug intoxication may persist for many days. Total apnea for five days and an isoelectric electoencephalogram for intervals up to 36 hours have been recorded with drug overdose patients who have survived without apparent neurologic sequelae. Continuing care should be provided in a medical intensive care unit with
Clinical Toxicology Downloaded from informahealthcare.com by University of Auckland on 12/06/14 For personal use only.
482
LETTER TO THE EDITOR
monitoring of temperature, blood pressure, pulse, respiratory rate, tidal volume, electrocardiogram, central venous pressure, fluid balance, electrolytes, and arterial blood gases with appropriate compensatory treatment for abnormalities. Intensive respiratory care should include frequent tracheal suction, frequent repositioning, and daily chest x-rays. Endotracheal tubes should be changed under supervision of an anesthesiologist. Tracheostomy should be performed only for surgical indications. Carefully attentive continuous nursing care is essential. COMPLICATIONS Aspiration pneumonia and subsequent infection is the most commonly occurring complication of coma secondary to drug overdose. Treatment consists of vigorous tracheal aspiration, periodic hyper inflation of lung, and antibiotic coverage. Rarely occurring are tension pneumothorax and renal failure of the crush syndrome type. Interstitial edema, including scleredema, is common in profound coma and usually represents increased capillary permeability rather than over hydration. Parenteral steroids may be helpful in this situation. Occasionally, interstitial edema is so severe as to compromise venous return and to require fasciotomies to provide venous drainage. Always be mindful that the patient may have sustained traumatic injury especially to the head, so be watchful for lateralizing neurologic signs. T O X I C O L O G I C ANALYSIS Any ingested material, initial gastric aspirate, and the first catheterized urine specimen all should be saved and labeled for laboratory examination with instructions to hold at least twentyfour (24) hours prior to discarding. Analysis of these fluids for drugs occasionally will change fundamental approach to treatment. Qualitative analysis provides confirmation of the clinical determination of etiology. Frequently multiple drugs are involved. Interpretation of quantitative findings is extremely difficult and usually is helpful only to follow the clearance of substances from the body. Previous drug use results in tolerance which prevents meaningful interpretation of absolute concentrations. Instructions for management of specific drugs identified should be consulted once symptomatic and supportive care is underway.
