Part 30 (1/2)

0.

0.

0.

2.7.1.1016 h after overdose 10.0.

2.0.

3.2.4.1.1624 h after overdose 4.1.3.1.2.1.1.0.

Nonnarcotic a.n.a.lgesic overdoses Total 24.1.5.1.5.5.12.2.Adapted from Riggs et al., 1989.

261.

262.

Drug overdoses during pregnancy Table 14.7 Case reports of aspirin overdose during pregnancy Amount EGA Case reports of aspirin overdose during pregnancy Amount EGA (weeks) Treatment Outcome Fetal Author ingested Maternal 100 5 grain 24.300 ml mg citrate Tinnitus, hyperventilated state Stillborn, anomalies Rejent and Baik, 1985 8 365 mg daily 37.Not mentioned Not mentioned Tachypnea, compensated Ahlfors et al., 1982 for several days metabolic acidosis up to delivery Megadose First trimester Not mentioned Not mentioned Metanephric adenoma Bove et al., 1979 Unknown 32.Not mentioned Uncomplicated Generalized hypertonia, Lynd, 1976 increased reflex, irritability 56 g daily 040 Not mentioned Abruptio placenta; C-section Unremarkable Levy et al., 1975 1518 g 40.Exchange Not mentioned Hyperpnoea, intercostal Earle, 1961 and suprasternal retractions present EGA, estimated gestation age.

Nonnarcotic a.n.a.lgesic overdoses 263.

Table 14.8 Recommended treatment of aspirin overdose Management Recommended treatment of aspirin overdose Management Early management Adult: >120 mg/kg: give 50 g activated charcoal.

Child: for >120 mg/kg give activated charcoal.

Consider charcoal even for late-presenting patients; peak absorption may be delayed up to 12 h postingestion especially with enteric coated tablets.

Adults only: > 500 mg/kg.

Consider gastric lavage followed by 50 g activated charcoal, if patient presents within 1 h.

Contact National Poison Information Service (NPIS) in the UK on 0870 600 6266 and in the US on 1-800-222-1222 Maintenance management Check salicylate concentration 4 h postingestion, then every 23 h until peak concentration achieved and is falling consistently. If history is reliable for an ingestion >120 mg/kg and tablets are enteric coated, consider measuring levels for minimum 12 h postingestion even if no salicylate is detected initially. Monitor and correct urine and electrolytes, arterial blood gases and pH, blood sugar, prothrombin time.

Rehydrate with oral or IV fluids; large volumes may be necessary to correct dehydration (care required with the elderly or those with cardiac disease). Moderate or severe cases may require central venous pressure monitoring particularly patients with cardiac disease or elderly people Repeat doses of activated charcoal (RAC) (adult, 2550 g; child, 1 g/kg) every 4 h until salicylate level has peaked and is consistently falling. RAC is effective in preventing excessive delayed absorption.

Urinary alkalinisation For salicylate level 500700 mg/L in adults or salicylate level 350600 mg/L in children/elderly where patients have moderate clinical effects. In the presence of alkaline urine (optimum pH 7.58.5), renal elimination of salicylate is enhanced (10- to 20-fold with an increase from a urine pH of 5 to 8). Forced alkaline diuresis is not recommended.

Adult: 1 L of 1.26 percent sodium bicarbonate (isotonic) + 40 mmol pota.s.sium IV over 4 h and/or 50 mL boluses of 8.4 percent sodium bicarbonate IV (ideally via a central line).

Child: 1 ml/kg 8.4 percent sodium bicarbonate saline infused at 23 mL/kg.h 1 mmol/kg pota.s.sium diluted in 10 mL/kg hypokalemia prevents urinary excretion of alkali so must be corrected. Check urinary pH hourly aiming for pH 7.58.5, the rate of bicarbonate administration alone (avoiding hyperkalemia) may need to be increased if pH remains <>

Check urine and electrolytes every 24 h and keep pota.s.sium between 4.0 and 4.5.

From Kamanyire, 2002.

conclusion as acetaminophen overdoses: early therapy antidote (activated charcoal, lavage, bowel irrigation) is a.s.sociated with better outcomes (Table 14.8).

Naproxen One case of naproxen overdose during pregnancy was published in detail. An estimated 8 h after maternal ingestion of 5 g of naproxen at 35 weeks of gestation, nonspecific and supportive antidote therapy was initiated because no specific antidote is available.

264.

Drug overdoses during pregnancy Following nonspecific therapy, spontaneous labor ensued and a preterm infant was delivered. The newborn had severe hyponatremia and water retention. Subsequently the infant recovered with no apparent sequelae at follow-up. The mother recovered with no evidence of hepatotoxicity or other adverse effects (Alon-Jones and Williams, 1986).

In contrast to the pharmac.o.kinetics of salicylate elimination, high doses of naproxen (14 g) result in a disproportionate increase in renal excretion of the drug without apparent saturation of the excretory mechanism or metabolic pathway (Erling and Strand, 1977; Runkel et al et al., 1976). Increase in renal elimination may contribute to a lower incidence of acute toxicity compared with salicylate overdose.

Ibuprofen Ibuprofen overdose during pregnancy has not been described in case studies and no specific antidote exists. Therefore, nonspecific antidote and supportive therapy should be given. Symptoms of ibuprofen toxicity include nausea, epigastric pain, diarrhea, vomiting, dizziness, blurred vision, and edema. The half-life of ibuprofen is 0.92.5 h in the post-absorptive period (Baselt, 1978). Among 67 cases of ibuprofen overdose, 36 percent occurred among children. Fifty reports of ibuprofen overdose during pregnancy have been reported, with mothers and infants suffering no untoward effects (i.e., hepatorenal failure, etc.) among those followed prospectively (Barry et al et al., 1984).

NUTRITIONAL SUPPLEMENT OVERDOSES.

Prenatal vitamins The course of pregnancy and infant outcome following prenatal vitamin overdoses has not been published. Since there is no specific antidote to prenatal vitamins, nonspecific and supportive antidote therapy should be given. It is reasonable to think that most cases of vitamin overdose would probably result in little, if any, risk to either mother or fetus. However, the retinoic acid content of the vitamins should be determined to estimate the total exposure. It is possible that megadose vitamin A may be involved, in which case Chapter 13, Use of dermatologics during pregnancy, should be consulted.

Iron The clinical course following iron overdose during pregnancy has been reported for six cases (Table 14.9). Notably, adverse outcomes were a.s.sociated with nonspecific treatment. The dangers of iron overdose vary according to the amount ingested. Iron poisoning is a.s.sociated with gastrointestinal hemorrhage, physiological shock, acidosis, hepatic failure, and coagulopathies (Table 14.10). Death is usually the result of liver failure or cardiac collapse. The highest serum iron concentrations are likely to occur within 4 h of ingestion, with serum levels in excess of 500 g/100 mL being more likely to be a.s.sociated with severe poisoning (James, 1970). Thus, these patients should be treated aggressively.

The specific antidote to iron overdose is deferoxamine. From clinical experience, it is clear that early administration of the antidote is essential if therapy is to be efficacious.

Table 14.9 Cases of iron overdose during pregnancy Amount Cases of iron overdose during pregnancy Amount EGA Treatment Outcome Fetus Author (weeks) Maternal 50 Ferrous gluconate tablets 27 Lavage, Deferoxamine Uncomplicated Uncomplicated Tran et al., 1998 40 Ferrous sulfate tablets 25.Deferoxamine Uncomplicated Uncomplicated Schauben et al., 1990 5 g Elemental iron (25 g 36.Deferoxamine Hepatic necrosis, coma and Uncomplicated Olenmark et al., 1987 ferrous sulfate) subsequent expiration in cardiac failure 50 300 mg Ferrous sulfate 15.Deferoxamine Temporary abdominal Uncomplicated Blanc et al., 1984 (3050 mg/kg Elemental tenderness and mild metabolic iron) acidosis Unknown amount, along 34.Deferoxamine Brief episodes of vomiting Uncomplicated Rayburn et al., 1983 with prenatal vitamins and mild pain Unknown amount 34.Deferoxamine ?.

Uncomplicated Rayburn et al., 1983 Nutritional supplement overdoses 95 tablets of Fer-In-Sol 14.Deferoxamine Died on the third day; pulmonary Spontaneous abortion Strom et al., 1976 edema and hypotension 90 325 mg Ferrous 16.Deferoxamine Metabolic acidosis, depressed Spontaneous abortion Manoguerra, 1976 sulfate capsules mental status; subsequent death 80 h postadmission 46 g Elemental iron with 10.DPTA.

Brief episode of abdominal pain, Uncomplicated Dugdale and Powell, 15 Sodium amytal, drowsiness, a systolic BP fall to 1964.

6 g Aspirin 60 mmHg EGA, estimated gestation age; DPTA, diethylenetriaminepentaacetic acid.

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Drug overdoses during pregnancy Table 14.10 Time course of iron overdose Time course of iron overdose Phase Time to onset Symptoms I.

03 h Vomiting, hemetemesis, abdominal pain, diarrhea, lethargy, restlessness II.

up to 12 h Quiescent period, symptoms subside III.

1248 h Shock, acidosis, hepatic necrosis, renal tubular necrosis, increasing lethargy, coma, seizures, hypotension, cyanosis, pulmonary edema, hypoglycemia, coagulopathies IV.

24 weeks Gastric scarring, gastric/pyloric strictures Adapted from Friedman, 1987.

Total iron-binding capacity and liver function should be routinely monitored in the patient with an iron overdose, as should thrombin and prothrombin times. Essentially, the gravida with an iron overdose should be managed similarly to the nonpregnant adult, as is described in detail elsewhere (Friedman, 1987). Guidelines for treatment according to ingested dose (if known) are given in Table 14.11. In a report of 49 pregnancies in which iron overdose occurred, there were 43 live births. Three infants had congenital anomalies, but they were exposed to the iron overdose and deferoxamine after the first trimester. Hence, the relations.h.i.+p appears not to be causal. The authors urge aggressive treatment of iron overdose with the specific antidote to prevent maternal death or organ toxicity (McElhatton et al et al., 1991a). Review of 61 pregnancies indicated that in iron poisoning during pregnancy (1) peak maternal serum iron levels are a.s.sociated with iron toxicity, and (2) deferoxamine should be administered without hesitation (Tran et al et al., 2000).

Table 14.11 Sequelae of iron overdose based on amount ingested Amount Sequelae of iron overdose based on amount ingested Amount Risk of toxicity Less than 20 mg/kg Minimal risk, no action required 2060 mg/kg Moderate risk, monitor for symptoms, induce vomiting More than 60 mg/kg High risk, requires treatment, gastrointestinal decontamination, chelation Adapted from Friedman, 1987.

Following unpublished animal studies that suggest deferoxamine may cause significant fetal effects in animals, clinical experience has not shown this to be true in the human. Iron-overdose-a.s.sociated pathophysiological effects on the mother seem to be the cause of adverse fetal outcomes, and not the direct result of iron overdose or antidote. No abnormalities have been reported among infants whose mothers consumed high doses of iron during pregnancy (Lacoste et al et al., 1992; Tenenbein, 1989). It appears as though the placenta acts as a partial barrier to iron (Olenmark et al et al., 1987; Rayburn et al et al., 1983; Richards and Brooks, 1966). Chemical properties of the deferoxamine molecule strongly suggest that it would not cross the placenta in large amounts because it is a large molecule (molecular weight, 657) and is highly polarized.

Hypnotic and sedative overdoses 267.

ANXIOLYTIC OVERDOSES.

Benzodiazepines Benzodiazepines are the most frequently used psychotropic medication in suicide gestures. The US Food and Drug Administration (FDA) approved a benzodiazepine receptor antagonist, flumazenil, in 1992 for the management of benzodiazepine overdose (The Flumazenil in Benzodiazepine Intoxication Multicentre Study Group, 1992; J Clin Pharmacol, 1992). Several investigators have shown the efficacy of flumazenil in revers-ing the clinical signs and symptoms of a benzodiazepine overdose (Krisanda, 1993; L'Heureux et al et al., 1992; Spivey et al et al., 1993). Flumazenil can cause complications (e.g., seizures) among patients with clinically high, but subtoxic, antidepressant poisoning or those who are taking benzodiazepines to therapeutically control seizures (The Flumazenil in Benzodiazepine Intoxication Multicentre Study Group, 1992; L'Heureux et al et al., 1992). One case study reported on the reversal of fetal benzodiazepine intoxication using flumazenil (Stahl et al et al., 1993). A 36-weeks, 22-year-old primipara ingested between 50 and 60 5 mg diazepam tablets. The patient was intravenously given two small doses (0.3 mg) of flumazenil. No adverse effects or withdrawal symptoms were noted in the patient or in the infant, who was born spontaneously 2 weeks later. The 'floppy infant syndrome' has been described, showing that benzodiazepines (1) cross the placenta and (2) have a depressive effect on the fetus. Warnings signs of complications in benzodiazepine overdoses in pregnancy are bradycardia and other symptoms of the drugs' depressive physiologic effects on mother and fetus.

Hydroxyzine The clinical courses of pregnancies after hydroxyzine overdoses have not been published. Hypersedation and hypotension are the most frequently observed abnormalities with hydroxyzine overdose in nonpregnant adults. Hydroxyzine counteracts epinephrine's pressor effect. Therefore, hydroxyzine overdose-a.s.sociated hypotension should not be treated with epinephrine. Intravenous fluids and other pressor agents (levarterenol or metaraminol) should be used instead to treat hypotension. Between 1 and 2 g of hydroxyzine pamoate commonly produces drowsiness and lethargy that may progress to a coma (Magera et al et al., 1981). Elimination half-life of hydroxyzine is 2.53.4 h, with a single dose of the drug and given that no more is taken (Baselt, 1978).