Physostigmine is a cholinergic agent that can be administered to reverse delirium associated with anticholinergic toxicity. However, it is infrequenly used since the reports of cardiac arrest in patients with TCA overdose.
A recently published study reviewed 161 articles – involving 2299 patients – to determine the adverse effects and their frequency after the administration of physostigmine.
Findings
Adverse effects were observed in 415 patients (18.1%)
Specific adverse effects
Of 394 TCA overdose, adverse effects occurred in 14 patients (3.6%)
Conclusion
Most clinicians are familiar with use of methylene blue for the treatment of methemoglobinemia, as a urinary analgesic, anti-infective, and anti-spasmodic agent, or for its use in endoscopy as a gastrointestinal dye, but this compound also has a role as a rescue antidote in life threatening poisonings causing refractory shock states and other shock states.
Bottom Line:
Methylene blue should be considered when standard treatment of distributive shock fails.
Therapeutic use or overdose of tramadol has been associated with seizure. However, it is unknown if there are any specific predisposing factor that increases a patient’s risk of seizure after tramadol use/overdose.
In a recently published study, eighty patient data with single ingestion of tramadol were reviewed.
Risk of seizure
Conclusion
In this small study, Asian patients and patients with abuse/misuse were at higher risk of developing seizure compared to patients who overdose tramadol.
Take home naloxone (THN) programs have been expanded to help reduce the opioid overdose-related deaths. A study was done in Australia to characterize a cohort of heroin overdose deaths to examine if there was an opportunity for a bystander to intervene at the time of fatal overdose.
235 heroin-overdose deaths were investigated during a 2 year study period in Victoria, Australia.
Conclusion
Taking a double-dose of a single medication is presumed to be safe in most cases. However, there is limited data to support this assumption.
A retrospective study of the California Poison Control System was performed to assess adverse effects of taking double dose of a single medication. During a 10-year period, 876 cases of double-dose ingestion of single medication were identified.
Adverse effects were rare (12 cases). However, medication classes that were involved in severe adverse effects included:
Conclusion:
Selective serotonin reuptake inhibitors are the most common anti-depressant used today. However, the use bupropion in adolescents is increasing due the belief that it has fewer side effects than TCAs.
Using the National Poison Data System (2013 – 2016), the adverse effects of bupropion were compared to TCA in adolescents (13 – 19 years old) with a history of overdose (self harm).
Common clinical effects were:
TCA: n=1496; Bupropion: n=2257
| Clinical effects | TCAs | Bupropion |
| Tachycardia | 59.9% | 70.7% |
| Drowsiness/lethargy | 51.5% | 18.1% |
| Conduction disturbance | 22.2% | 15.6% |
| Agitation | 19.1% | 16.4% |
| Hallucination/delusions | 4.2% | 23.9% |
| Seizure | 3.9% | 30.7% |
| Vomiting | 2.7% | 20.0% |
| Tremor | 3.7% | 18.1% |
| Hypotension | 2.7% | 8.0% |
| Death | 0.3% | 0.3% |
Conclusion:
Bupropion overdose results in significant adverse effects in overdose; however, death is relatively rare.
Alcohol withdrawal syndrome is frequently treated with benzodiazepines following CIWA-Ar (Clinical Institute Withdrawal Assessment of Alcohol scale). There are other medications that are used as either second line or as adjunctive agents along with benzodiazepines. A retrospective study compared the clinical outcomes between phenobarbital vs. benzodiazepines-based CIWA-Ar protocol to treat AWS.
The primary was ICU length of stay (LOS); secondary outcome were hospital LOS, intubation, and use of adjunctive pharmacotherapy.
Study sample: 60 received phenobarbital and 60 received lorazepam per CIWA-Ar.
Phenobarbital protocol:
Results
|
| Phenobarbital | CIWA-Ar |
| ICU LOS | 2.4 days | 4.4 days |
| Hospital LOS | 4.3 days | 6.9 days |
| Intubation | 1 (2%) | 14 (23%) |
| Adjunctive agent use | 4 (7%) | 17 (27%) |
Conclusion
Phenobarbital therapy appears to be a promising alternative therapy for AWS. However, additional studies are needed prior to adapting phenobarbital as first line agent for AWS management.
The management of pediatric hydrocarbon ingestion has not changed significantly over the past several decades. One of the earlier study that helped established the management approach is by Anas N et al. published in JAMA, 1981.
It was a retrospective study of 950 children who ingested household hydrocarbon containing products.
Discharged patients: n=800
Admitted patients: n=150
This study recommended that hospitalization is required in patients…
CHS Treatment:
Bottom line: Patient education should be provided on the paradoxical and recurrent nature of the symptoms of CHS to discourage relapse of use often stemming from false preception of beneficial effects of cannabis on nausea.
A 19 year old male presents confused and very agitated complaining of seeing things and stomach pain. His friends report he ingested a naturally occurring plant to get high a few hours ago but is having a "bad trip". His physical exam :
Temp 100.3, HR 120, RR 14, BP 130/88. Pulse Ox 98%.
Skin: Dry, hot , flushed
HEENT: Marked mydriasis 6mm
Lungs: Clear
Heart: Tachycardic
Abdomen: Distended tender suprapubic with absent bowel sounds,
Neuro: Extremely agitated pacing, no muscular rigidity.
What has he ingested and what is the treatment?
Analphylatoid reaction is caused by non-IgE mediated histamine released. Intravenous N-acetylcysteine (NAC) infusion is well known to cause analphylatoid reaction. However, it’s incidence is unknown.
Recently, a large retrospective study of all patients who received 21-hour IV NAC in 34 Canadian hospitals (1980 to 2005) was performed.
Anaphylactoid reaction was documented in 528 (8.2%) of 6455 treatment courses
Over 90% patients developed analphylatoid reaction within 5 hours.
Onset of reaction:
Administered medication for treatment
Patient characteristics that were associated with higher incidence of Anaphylactoid reaction includes
Bottom line
A 68 year old male presents to the ED complaining of weakness to his legs. He states today his yard chores took him over 2 hours to complete instead of the usual 15-20 minutes due need to take frequent breaks for rest due to leg pain. He denied any chest pain or shortness of breath. Past medical history included hypercholesteremia, HTN, and CAD. He is taking aspirin and recently started on rosuvastatin.
His physical exam was unremarkable.
Results showed normal EKG and CBC. Bun was 70, Creatinine was 3.4, and CPK of 1025.
This patient has statin induced rhabdomyolysis and acute renal failure.
Take Home Points:
Various intial doses of naloxone (0.4 to 2 mg) are administered to reverse the signs and symptoms of opioid toxicity. However, there is limited data regarding the duration of action of naloxone is correlated to the administered dose.
A recently published retrospective study investigated whether initial naloxone doses (IV), low-dose (0.4 mg) vs. high-dose (1-2 mg), lead to different time to recurrence of opioid toxicity.
Study sample: 274 patient screened but 84 patients were included.
Higher rate of adverse effects (withdrawal symptoms - vomiting, agitation, tachycardia, etc.) were observed in high-dose group (41% vs. 31%) but this was not statistically signficant.
Conclusion:
Elevated transaminases are found in both rhabdomyolysis and delayed acetaminophen (APAP) toxicity. Establishing the cause of elevated transaminase can be difficult when there is unclear history of acetaminophen ingestion.
A retrospective study of patients with delayed acetaminophen toxicity or rhabdomyolysis from 2006 to 2011 was recently published.
The authors compared AST/ALT, CK/AST and CK/ALT ratio of
Results
AST/ALT ratio
CK/AST ratio
CK/ALT ratio
Conclusion
Sulfonylureas are commonly used oral hypoglycemic agents for type II diabetes. Agents on the market include glipizide (Glucotrol), glyburide (Micronase, Glynase, Dibeta) and glymepiride (Amaryl). These agents exert their effect by stimulation of insulin release from the pancreatic beta islet cells. Following overdose, hypoglycemia is usually seen within a few hours of ingestion and can be prolonged and profound. First line treatment for rapid correction of severe hypoglycemia is administration of an intravenous bolus of concentrated dextrose. However, use of dextrose infusion in attempt to maintain euglycemia is problematic as it can cause further release of insulin and rebound hypoglycemia. Octreotide ia a long acting synthetic somatostain analogue, blocks insulin secretion and has been shown to prevent recurrence of hypogylcemia better than placebo.
Bottom Line:
From 1960s to 1970s, physostigmine was routinely administered as part of the "coma cocktail." Since the publication of two cases by Pentel (1980) that resulted in asystole after administration of physostigmine in TCA poisoned patient, its use has declined significantly.
However, physostigmine still possess limited but clinically useful role in the management of patients with antimuscarinic/anticholinergic induced delirium.
Recently, a prospective observational study was performed in the use of physostigmine when recommended by a regional poison center.
In 1 year study period, physostigmine was recommended by a regional poison center in 125 of 154 patients with suspected antimuscarinic/anticholinergic toxicity.
common exposures were
57 of 125 patients received physostigmine per treating team.
Of the remaining patients,
Delirium control
Adverse events (physostigmine group vs. non-physo group) - no statistically significant difference.
Conclusion:
Physostigmine can safely control antimuscarinic/anticholinergic-induced delirium.
Acutely agitated patients in the emegency room receive single or combination of benzodiazepine (lorazepam vs. midazolam) and antipsychotic (e.g. haloperidol) agents. Recently, use of ketamine has also been advocated to sedate agitated patients.
A recently published article compared IM administration several medications to treat acutely agitated patients in the ED. According to established protocol, each medication was administered in predetermined 3 week blocks:
Results
N=737 with median age of 40 years, 72% men.
Midazolam resulted in greater proportion of patients with "adequate" sedation (altered mentatl status scale <1) compared to antipsychotics at 15 min post administration. Among antipsychotics, olanzapine resulted in greater proportion of patient with sedation.
Adverse effect were limited
Conclusion:
Midazolam 5 mg IM achieve more effective sedation at 15 min in agitated ED patients than antipsychotics.
Methylene Blue is a dye that was synthesized in the late 1800s as an antimalarial drug. After the emergence of chloroquine its use loss favor partly due to unpopular side effects of temporarily turning the urine, other body fluids, and the sclera blue. Methylene blue is primarily known as a highly effective fast acting antidote for methemboglobinemia. Over the past few years, it has become an important therapeutic modality with expanding uses in cardiac surgery and critical care. As a potent inhibitor of nitric oxide mediated guanylate cyclase induced endothelium vascular smooth muscle relaxation, it has been shown to be effective in increasing arterial blood pressure and cardiac function in several clinical states, such as septic shock and calcium channel blocker poisoning.
BOTTOM LINE:
Methylene blue should be considered for treatment of refractory shock from calcium channel and beta blocker poisoning.
Clinical improvement in refractory hypotension and reduction of vasopressor dose has been described in several poisoning cases.
Recommended dose is 1–2 mg/kg injection with effects seen within 1 hour.
On May 3, the FDA approved adexanet alfa, the reversal agent for factor Xa inhibitors - apixaban and rivaroxaban. It received both U.S. Orphan Drug and FDA Breakthrough Therapy designations.
Unlike indarucizumab (a monoclonal antibody fragment) to reverse dabigatran (direct thrombin inhibitor) associated bleeding, adexanet alfa is a recombinant modified human factor Xa decoy protein.
A phase 3 study showed that adexanet alfa decreased the anti-factor Xa activity of rivaroxaban by 92% from baseline and by 94% in apixaban treated participants.
ANNEXA-4 study involving participants with acute major bleeding (GI and intracranial) showed a significant decrease in the anti-factor Xa activity after the bolus dose of adexanet alfa and "effective" hemostasis was noted in 79% of the participants at 12 hours post infusion.
Andexanet alfa is expected to become available in June 2018.
Despite initial excitement for the use of intravenous lipid emulsion (ILE) therapy as an antidote for serious poisonings due to lipohphilic drugs there remains an absence of evidence combined with an incomplete understanding of its efficacy, mechanisms of action, safety, and analytical interferences to recommend its use except in a few clinical scenarios.
The lipid emulsion workgroup performed a comprehensive analysis of four systematic reviews and based recommendations from consensus of expert panelists from the American Academy of Clinical Toxicology, the European Association of Poison Centres and Clinical Toxicologists, the American College of Medical Toxicology, the Asia Pacific Association of Medical Toxicology, the American Association of Poison Control Centers, and the Canadian Association of Poison Control Centers. Toxins evaluated had to have a minimum of three human cases reported in the literature.They concluded that ILE could be indicated for the following clinical situations:
The Bottom Line:
The use of Intravenous Lipid Emulsion in severe poisoning is recommended only for a few poisoning scenarios and was based on very low quality of evidence, and consideration of risks and benefits, adverse effects, laboratory interferences as well as related costs and resources.
