Dose it Right!

Dose it Right ! cont'

Thank you all for the excellent comments

Yes this patient had rhabodmyolysis and AKI , probably from being down for long time after the opioid overdose , but the agitation resulting from the withdrawal due to high doses of naloxone made it worse

Optimal Naloxone dosing for reversal of opioid overdose have been controversial and it is hugely based on clinical judgment .The administration of naloxone presents a challenge of balancing opposing outcomes, namely the reversal of opioid toxicity while avoiding opioid-withdrawal syndrome.

Current evidence suggests that in the hands of trained medical personnel capable of advance life support and airway intervention and for the avoidance of withdrawal by utilizing a small initial dose of naloxone is safe.

However, in the hands of laypeople or those without adequate training or equipment to provide prolonged respiratory support, the risk of under-dosing naloxone far outweighs the potential risks of precipitating opioid withdrawal.

Complication Of Naloxone :!

I agree that opioid withdrawal is rarely life threatening , although naloxone have been linked to pulmonary edema , many published case reports illustrate the potential risk of pulmonary edema with opioid toxicity and not necessary as a result of naloxone . Dysrhythmias and seizures have also been reported; however, the distinction between the opioid-induced hypoxia, the patient’s underlying disease, and the effects of naloxone is difficult.

There was clinical trial comparing the two dosing regimen of naloxone ;

Group 1 ( Tintinally )received naloxone with the dose 0.1 mg given every two to three minutes while group 2 ( Goldfrank )received naloxone with the initial dose of 0.04 mg increasing to 0.4, 2, and 10 mg every two to three minutes to reverse respiratory depression

They were then compared regarding reversal of toxicity and risk of development of complications.. They found , the time to reversal of the overdose signs/symptoms was significantly less in Goldfrank regimen protocol (P<0.001). Frequency of withdrawal syndrome and recurrence of respiratory depression were not significantly different between the two groups. Aspiration pneumonia and intubation were more frequent in group 2 and their conclusion

Conclusion: It seems that gradual titration of naloxone by Tintinalli protocol can reduce major complications compared to the Goldfrank regimen. However, this protocol was not perfect in opioid-dependent methadone-overdosed patients, either, since it could induce complications, as well. We may need new protocols in overdosed opioid-dependent patients.

In general i will advice starting with 0.4 mg for apneic patient until u get response and then titrate the repeat doses to a smaller dose of 0.1 mg . If repeated doses needed an infusion equal to two-thirds this initial dose per hour should suffice to prevent recurrence of respiratory depression

References

1. . Juliana Lombardi, Eric Villeneuve, , Sophie Gosselin In Response to: “The Evolution of Recommended Naloxone Dosing for Opioid Overdose by Medical Specialty J Med Toxicol. 2016 Dec; 12(4): 412–413. Published online 2016 Oct 24. doi: 10.1007/s13181-016-0591-3

2. Khosravi et al.Comparison of Two Naloxone Regimens in Opioid-dependent Methadoneoverdosed Patients: A Clinical Trial Study Current Clinical Pharmacology Volume 12 , Issue 4 , 2017 DOI : 10.2174/1574884713666171212112540

3. Rachael Rzasa Lynn and JL Galinkin Ther Adv Drug Saf. 2018 Jan; 9(1): 63–88.Published online 2017 Dec 13. doi: 10.1177/2042098617744161Naloxone dosage for opioid reversal: current evidence and clinical implications

4. Goldfrank Toxicology

Post-naloxone Care:

Observe patients for at least 2 hours after the last dose of naloxone was given to assess for recurrent opioid toxicity. Reassess for sedation, respiratory depression, medical complications of overdose and/or drug use (aspiration, pulmonary edema, rhabdomyolysis, compartment syndrome, infections).

If naloxone is overdosed, it can cause opioid withdrawal, which is almost never fatal but is very uncomfortable for the patient. While pulmonary edema is recognized as a side effect of naloxone, it is rare and may be due to other co-morbid factors in the opioid overdose patient.

The goal with naloxone administration is to avoid worsening respiratory depression, aspiration and cardiac arrest on the one hand, while on the other hand avoiding sending the patient into severe opioid withdrawal and an agitated state.

Targets of naloxone dosing

• RR>12

• SpO2 >90%

• EtCO2 <45

While traditional teaching suggested 0.04mg IV q3mins until response, with fentanyl analogues, patients often require as much as 12mg of naloxone. Therefore current dosing recommendations are:

First dose: 0.4mg IV/IM followed by 1mg in 3 minutes if no response.

Then double the dose q3mins until targets are reached as outlined above.

If >12mg naloxone have been given without achieving the above targets, consider endotracheal intubation and mechanical ventilation. Earlier intubation may be required.

Q1 Why did he became agitated and how could you avoid it?

- Opioid withdrawal symptoms... the patient presented to ED with typical toxidrome of opioids overdose.

History of the uses would be the key to the rate of naloxone administration in such cases. Further hx from his friend is needed wither this patient is a first-time user (naive) or chronic user of opioids.

Despite our reference books recommend using bolus doses (2mg IV every 5-minute max 10 mg) in the apneic and near-apneic patients (like in this case). The risk of withdrawal symptoms will be higher if used in chronic users. In this case, I suggest starting smaller doses. They can start at 0.2 mg every 5 minutes and wait for the effect. repeat the dose accordingly. they can initiate the infusion therapy if the patient required multiple doses.

Airway support is required.

Q2 What are the expected complications in this patient?

- altered mental status

- Agitation

- Seizure

- Rhabdomyolysis

Pt had acute withdrawl of opiod unknown if he is dependant on morphine or not .

, so using smaller doses of naloxone 0.1 to 0.2 after the initial higher dose 0.4 , the agitation and seizure causing rhabdomaylsis noted as myoglobinurea