Chapter 27 – Drug Overdose in Pregnancy




Abstract




Key Implications





Chapter 27 Drug Overdose in Pregnancy



Lakshman Karalliedde




Key Facts




  • Intentional overdoses (i.e. suicide rates due to drug overdose) are low and generally result in low toxicity to the mother.



  • The risk of overdose is highest during the first few weeks of pregnancy and the first pregnancy, low socioeconomic status and in those who abuse ethanol.



  • Antipyretics, analgesics and anti-rheumatics are the most common drugs ingested.



  • Adverse birth outcomes such as preterm labour and low birth weight have been reported in a very small number of patients. Most drug overdoses require only supportive care. However, a few drugs which may cause severe overdose are discussed in this chapter. Treat the poison if an antidote is available, as the ‘poison’ is bound to be more toxic than the antidote to the fetus.



  • Physiological changes in pregnancy may be associated with changes in pharmacokinetics and toxicokinetics following overdose. The delay in gastric emptying time of up to 50% would result in lower peak plasma concentrations. Similarly, the increase in plasma volume during pregnancy and the associated increase in the volume of distribution would also result in reduced peak plasma concentrations of the drug.



Key Implications




  • Maternal: Some pharmaceutical agents may induce renal, liver and cardiac malfunction.



  • Fetal: Effects on the fetus following overdose of the mother are sparse or non-existent at present.



  • Often effects on the fetus are considered to be directly related to maternal outcome.



  • Some drugs are known to be mutagenic and/or teratogenic. Others have the potential to be carcinogenic.



Key Diagnostic Signs


These depend on the class of drug/s ingested. Always suspect poisoning when the presenting physical signs are not commonly associated with known disease states.


Some examples:




  • Anticholinergic signs: dilated pupils, sweating, warm and red peripheries – for example tricyclic antidepressant or belladonna alkaloid self-poisoning



  • Sympathomimetic signs: tachycardia, high blood pressure, sweating, dilated pupils – overdose of sympathomimetics, for example, amphetamines



  • Increased respiratory rate, sweating and tinnitus – salicylate self-poisoning



  • Bradycardia and hypotension – calcium channel blocker or beta-blocker self-poisoning



  • Depressed respiration, consciousness and small pupils – opioids (pinpoint pupils) or benzodiazepines self-poisoning



  • Hyperthermia and rigidity – selective serotonin reuptake inhibitors (SSRIs)



  • Hypoglycaemia – self-poisoning with anti-diabetic medications



Key Actions



Assess and Stabilise the Patient


Drug overdose should be treated as a medical emergency. Attend to the patient immediately and stabilise (maintain vital physiological parameters, e.g. oxygen saturation, blood pressure) the patient as a priority (Table 27.1).




Table 27.1 Clinical signs and management summary of some commonly ingested pharmaceutical agents





























































































































Drug class Clinical effects Toxic dose Action Comments
ACE inhibitors Hypotension and tachycardia. Hyperkalaemia Variable Supportive care. Intravenous fluids
Amiodarone Non-specific ECG changes, hypotension and bradycardia Variable AC and supportive care
Antihistamines Nausea, vomiting, retention of urine, tachycardia

Cyclizine 5 mg/kg, Diphenhydramine


>300 mg

Activated charcoal (AC) and supportive care
Antibiotics Mainly gastrointestinal – variable signs depending on the agent AC and supportive care Some are teratogenic
Anticoagulants (warfarin) Bleeding tendency and prolonged international normalised ratio (INR) Variable AC and vitamin K for up to 10 days If mother is on long-term warfarin, correction should be gradual to prevent thrombosis
Barbiturates Nystagmus, ataxia, small pupils, respiratory depression and coma Manage airway. AC
Benzodiazepines CNS and respiratory depression Variable Manage airway. AC Do not give flumazenil
Bromocriptine Nausea, vomiting and hypotension. Psychosis and hallucinations 50–75 mg AC. IV fluids and supportive care
Clonidine Drowsiness, coma, bradycardia and hypotension. Hypertension Variable AC. Supportive care, IV fluids
Ergotamines Cold cyanotic peripheries, abdominal pain Variable AC, glyceryl trinitrate, nitroprusside and nifedipine Increases uterine tone, fetal hypoxia
Lithium (acute ingestions) Nausea, vomiting, ataxia, myoclonic twitches, confusion and coma

Whole bowel irrigation if >4 g of sustained release is ingested. Do lithium levels at 6 hours post ingestion.


Observe for up to 24 hours. Manage airway and fluid balance


May induce congenital malformations.


Haemodialysis if coma, convulsions and respiratory failure or levels >7.5 mmol/L

MAOI Drowsiness, confusion, agitation, coma, hypertension, hyperthermia Airway management, diazepam, fluids Symptoms may occur 24 hours post-ingestion
Opioids Drowsiness, respiratory depression, hypotension, pinpoint pupils, coma AC, naloxone (0.4 mg IV, increased every 2–3 minutes to a maximum bolus dose of 2 mg – use 2/3 the dose required as a maintenance each hour), airway management Observe for minimum of 6 hours. In addicted patients, naloxone may precipitate withdrawal

Non-steroidal


anti-inflammatory drugs

Variable – no symptoms to CNS depression and acidosis in massive doses Variable AC, supportive care
SSRI Nausea and vomiting. AC. In serotonin syndrome –
Drowsiness and serotonin cooling, IV fluids, sedate with
syndrome (hyperthermia,rigidity, rhabdomyolysis) diazepam and cyproheptadine
Theophylline Nausea, vomiting, tachycardia, convulsions, hypokalaemia 1 g Multiple dose AC Observe 4 hours or up to 24 hours if sustained-release drug is ingested


Use Standard Advanced Cardiac Life Support





  • Assess airway, breathing and circulation – use standard guidelines.



  • Assess airway – talk to the patient. If she responds, the airway is patent. If there is no response, carry out airway opening manoeuvres (head tilt and jaw thrust).



  • Assess breathing – look, feel and count respiratory rate – feel for air on palm. Cyanosis?



  • Assess circulation – presence of pulse, measure blood pressure.



  • Assess neurological disability – note score on Glasgow Coma Scale (GCS).



  • Connect the patient to an ECG monitor and pulse oximeter. Measure blood sugar and serum electrolytes.



All patients who present with a ‘threatened airway’ (i.e. at risk of aspiration into the lungs) and low GCS score should have endotracheal intubation.



Assess Risk




  • Ask for the name of the drug/s.



  • Determine number of tablets, strength and preparation (ordinary release or slow release).



  • Decide if the ingested dose is likely to cause toxicity. Examine to detect the presence of signs of toxicity.



  • In the absence of signs of toxicity, assess the probability of subsequent development of toxicity.



  • Observed for widened QRS (100 ms) complex on the ECG in patients with tricyclic antidepressant poisoning. Similarly, observe for bradycardia and heart blocks in patients with calcium channel blocker and beta-blocker poisoning.



  • Observe for tachyarrhythmias in patients with tricyclic antidepressants (TCA), digoxin poisoning.



  • Patients with beta-blockers poisoning are at increased risk of Prolonged QT interval. Similarly metabolic acidosis may occur in patients with metformin poisoning (lactic acidosis), and salicylate and iron poisoning.



Decontaminate




  • Decontamination may be effective for longer periods than the usually recommended 1 hour post-ingestion.



  • Gastric lavage is not routinely recommended for a pregnant patient with drug overdose. Use activated charcoal.


For ordinary-release medications in overdose:




  • Administer activated charcoal 1 g/kg (50 g) if the patient presents within 1 hour post-ingestion.



  • The patient should have a protected airway and a verbal or written consent should be obtained for this if the clinical situation (i.e. conscious level) permits



  • Multiple doses of activated charcoal may be given in some cases of overdose with drugs such as carbamazepine and salicylates [1].



  • Whole bowel irrigation should be carried out following overdose with drugs such as slow-release calcium channel blockers, lithium and iron.



  • Method: Administer 1 L of oral polyethylene glycol hourly until the rectal effluent is clear.



Confirmation of Poisoning


Serum drug assays – limited use but a necessity in some instances, for example, instances e.g. overdose with paracetamol, iron, salicylates, digoxin or lithium.


Other indicators of toxicity, for example:




  • ECG: widened QRS (100 ms) complex in tricyclic antidepressant poisoning. Bradycardia and heart blocks in calcium channel blocker and beta-blocker poisoning.



  • Tachyarrhythmias in tricyclic antidepressants (TCA), digoxin poisoning.



  • Prolonged QT interval – beta-blockers poisoning.



  • Metabolic acidosis – metformin poisoning (lactic acidosis), salicylate and iron poisoning.



Give Antidotes


Some drug overdoses should be treated using specific antidotes.



Paracetamol



Mechanisms of Toxicity

Paracetamol is largely metabolised in the liver to non-toxic glucuronide (60%) and sulphate (30%) conjugates, which are subsequently excreted in the urine.


A small fraction is also converted (by cytochrome P450-dependent mixed function oxidase enzymes) to the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). The toxic metabolite is inactivated by conjugation with hepatic glutathione and eventually excreted as cysteine and mercapturic acid conjugates. In overdose, there is accumulation of this toxic metabolite.


In healthy women, a dose greater than 200 mg/kg or 10 g in total (whichever is less) may be hepatotoxic. In those considered as high-risk, that is, malnourished patients, patients on enzyme-inducing drugs (e.g. carbamazepine, phenytoin, rifampicin) or patients suffering from HIV, liver toxicity may occur at lower doses. The risk of liver damage is assessed using the paracetamol normogram (Figure 27.1) which plots the plasma paracetamol concentration in relation to the time of ingestion.





Figure 27.1 Paracetamol normogram.


Those on or above the treatment line will require treatment with N-acetylcysteine (NAC), without which severe liver damage could be expected in approximately 60% of patients. Where paracetamol has been taken chronically or in a staggered manner (e.g. >2 hours between doses), or where the time of ingestion is unknown, the plasma paracetamol concentration cannot accurately be interpreted using the normogram. If the total dose in 24 hours exceeds 200 mg/kg or 10 g, whichever is the smaller (> 100 mg/kg in high-risk patients), NAC should be administered.



Investigations


Measure plasma paracetamol level 4 hours after ingestion. Obtain baseline values for INR, serum creatinine, aspartate transaminase (AST) and alanine transaminase (ALT).


A specialist liver centre should be contacted if




  • The INR is >2 at 24 hours; >4 at 48 hours; >6 at 72 hours post-ingestion


         OR



  • The PT in seconds is greater than the number of hours since overdose


         OR



  •   if the patient has any of the following:



  • An elevated plasma creatinine (>200 μmol/L).



  • Hypotension (mean arterial pressure less than 60 mm Hg) following accepted methods of resuscitation.



  • Encephalopathy.



Treatment

It is important to treat within 8 hours post-ingestion, as the recovery is almost 100% in this case. If a plasma paracetamol level could be obtained within 8 hours, start treatment after the plasma paracetamol level is available. If the level is unlikely to be available within 8 hours of ingestion, start treatment when the ingested dose is considered potentially toxic. Continue/discontinue treatment after receiving the plasma paracetamol level.


NAC is the antidote and it should be administered as follows:




  • 150 mg/kg body weight in 200 mL of 5% dextrose by slow IV infusion over 15 minutes, followed by



  • 50 mg/kg by IV infusion in 500 mL of 5% dextrose over 4 hours and 100 mg/kg in 1 L of 5% dextrose over the next 16 hours.


Two hours after completion of the infusion, repeat measurements of INR, serum creatinine and AST. If the INR is stable or declining, there is no need for further treatment with NAC. If the patient is symptomatic and has an elevated INR, the patient is likely to require further doses of NAC.

Only gold members can continue reading. Log In or Register to continue

May 9, 2021 | Posted by in OBSTETRICS | Comments Off on Chapter 27 – Drug Overdose in Pregnancy
Premium Wordpress Themes by UFO Themes