Article

Oral pure tramadol exposure like other opioids can cause apnea- why not be careful?

410 Correspondence

References

  1. Hassanian-Moghaddam H, Farajidana H, Sarjami S, et al. Tramadol- induced apnea. Am J Emerg Med 2012. http://dx.doi.org/ 10.1016/j.ajem.2012.05.013.
  2. Emamhadi M, sanaei-Zadeh H, Nikniya M, et al. electrocardiographic manifestations of Tramadol toxicity with special reference to their ability for prediction of seizures. Am J Emerg Med 2012. http:

//dx.doi.org/10.1016/j.ajem.2011.12.009.

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  3. Farajidana H, Hassanian-Moghaddam H, Zamani N, et al. Tramadol- induced seizures and trauma. Eur Rev Med Pharmacol Sci 2012; 16(Suppl 1):34-7.
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Oral pure tramadol exposure like other opioids can cause apnea- why not be careful?

To the Editor,

I appreciate the opportunity and respond to some criticism that has targeted our study regarding “Tramadol-induced apnea” [1,2]. First of all, the retrospective nature of our study imposes some limitations, which are inevitable, and coin- gestants cannot be fully ruled out. Nonetheless, there is some evidence and strengths, which suggests that these cohort data are reliable.

Pure tramadol overdose in our study was defined based on

3 parameters in retrospective chart reviews: first, taking history on admission; second, urine drug Screening tests; and finally, in-depth psychiatric interview with the patients and their relatives who clarified Drug history or using coingested drugs before admission. All patients were included in the study if those 3 parameters were not mismatched. Although we were not be able to confirm all Eliza urine screens (including drug of abuses by other laboratory methods), we

were able to quantify all sedative hypnotics particularly in complicated cases such as apnea when appropriate. In addition, even in noncomplicated cases, negative results are more sensitive for ruling out probable coingestants.

We never claim that “it does not seem that there is an association between apnea and mortality due to the oral consumption of tramadol.” Quite the opposite, what we state is that “the mortality from tramadol poisoning appeared to be increased in those patients with apnea although overall numbers were low,” and further study is suggested.

We have a similar scenario in a pediatric group, those who ingest tramadol accidentally, and coingestions are far from mild. In the near future, on November 2012 annual APAMT meeting in Hong Kong, we are reporting 20 cases of child oral tramadol exposure, of whom 3 (15%) experienced apnea and respond to naloxone.

Considering opioid properties of tramadol, lack of Respiratory effects of pure tramadol overdose in the literature should be more discussed. There were few available studies directly pointing to respiratory depression and apnea in human oral tramadol exposure [3-5]. So, it was logical to consider all probable involved mechanisms in our study and expand its explanations including ultra-rapid metabolizers.

On the other hand, similar to other causes of Epileptic seizure, short bouts of apnea are common during motor (Grand mal) seizures (“apneic seizure”). However, if one looks at Table 2 again, 3 of 18 patients experienced apnea without seizure. So still, we had some patients who did not convulse despite apnea, and one of them died while not intubated because he did not need to be intubated based on assessing consciousness level and lack of prominent central nervous system depression.

From clinical view, as a clinical toxicologist, I prefer to be more conservative in these cases. In the emergency department, we usually do not know who takes tramadol as the sole drug or coingestants (particularly given the high incidence of tramadol abuse with other opioids/sedative hypnotics). Apart from current challenges, I think most physicians believe that oral tramadol solely or in combina- tion with other sedative drugs can induce respiratory depression and apnea. In each circumstance, we should be aware of probable respiratory depression and estimate further risks of adverse health outcomes. In conclusion, it is logical to state that “oral pure tramadol exposure like other opioids can cause apnea, why not? Be careful.”

Hossein Hassanian-Moghaddam MD Toxicological Research Center Loghman-Hakim Hospital Department of Clinical Toxicology

Shahid Beheshti University of Medical Sciences

Tehran, Iran E-mail addresses: [email protected]

[email protected] http://dx.doi.org/10.1016/j.ajem.2012.08.020

Correspondence

References

  1. Hassanian-Moghaddam H, Farajidana H, Sarjami S, et al. Tramadol- induced apnea. Am J Emerg Med 2012. http://dx.doi.org/10.1016/ j.ajem.2012.05.013.
  2. Sanaei-Zadeh H. Oral tramadol-induced apnea: incidence and associ- ation between this type of apnea and mortality? Am J Emerg Med 2012. http://dx.doi.org/10.1016/j.ajem.2012.08.021.
  3. Nieuwenhuijs D, Bruce J, Drummond GB, Warren PM, Dahan A. Influence of oral tramadol on the dynamic ventilatory response to carbon dioxide in healthy volunteers. Br J Anaesth 2001;87(6):860-5.
  4. Spiller HA, Gorman SE, Villalobos D, Benson BE, Ruskosky DR, Stancavage MM, et al. Prospective multicenter evaluation of tramadol exposure. J Toxicol Clin Toxicol 1997;35(4):361-4.
  5. Hassanian-Moghaddam H, Rashidi B. Mortality and complication associated with acute tramadolintoxication. Seville, Spain: EAPCCT XXVIII International Congress; 2008.

When health care priorities are unclear: do we obtain organs or try to save lives?B,BB

To the Editor,

In the comment entitled “When health care priorities are unclear: do we obtain organs or try to save lives?,” the authors (curiously none of them is a medical doctor) review a set of ethical principles, which should be guiding the practice of donation after death has been determined by circulatory criteria in persons whose death has occurred after an unexpected out-of-hospital cardiac arrest [1].

Currently also implemented in France, Italy, and the Netherlands among others, Spain was one of the countries first developing protocols allowing Organ donation to occur from persons whose death had resulted from an unexpected cardiac arrest, this taking place either in the out-of-hospital setting or within the hospital [2]. Starting in the 90s, these protocols have allowed the transplantation of 1361 kidneys, 133 livers, and 52 lungs in our country, with excellent results in the case of kidney transplants and promising outcomes in liver and lung transplantation [3-7]. Over the years, the programs have been extending throughout the country with an excellent acceptance by the entire professional network and an adequate public perception, as made evident by the high consent rate in this type of donation [8]. Its practice has been based on a specific legislation in place since 1999 and on national consensus documents released in 1996 and recently in 2012 and developed with the active participation of all relevant national professional societies in the field of emergency and intensive care [9-11].

Contrary to what is stated, uncontrolled Donation after circulatory death (DCD) is only activated when all appropriate therapeutic possibilities have been applied and resulted unsuccessful, strictly following local protocols according to

? No grants or financial support.

?? Uncontrolled donation after circulatory death: in the donor’s best interest.

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the National Cardiopulmonary Resuscitation Plan, aligned with international professional standards–those mentioned by the authors [12,13]. Such protocols are applied by highly qualified and trained emergency medical teams and are exactly the same, regardless of the engagement of the team in a DCD program and regardless the patient is to be potentially considered a donor should the measures fail. Protocols in place always include the treatment of the known or suspected cause of the cardiac arrest. It is only after further treatment is deemed futile under the light of the mentioned standards– termination of resuscitation rules–when uncontrolled DCD protocols are considered. Should the treatment of out-of- hospital cardiac arrest not be optimal, the corresponding health care quality indicators of the Spanish emergency services would not place our country in a position of excellence [14,15]. The authors propose the option of nonconventional Resuscitation procedures (NCRPs) to be incorporated to the standards of care in cases of unexpected cardiac arrest. Of note, not all procedures referred in the article as such are considered NCRP: some of them are conventional resusci- tative measures, others are specific measures applicable in special situations, and some are only applicable in patients with spontaneous recovery of circulation (ie, hypothermia). Contrary to what is suggested, pure NCRPs are not recommended in current international guidelines because the effectiveness of these emerging protocols is still to be proven and their proportionality evaluated. Moreover, far from being effective, some of the proposed measures have proven to be harmful in international multicentric randomized clinical trials, references curiously obviated in the article [16]. If the limited and contradictory available evidence is enough for the authors to call countries with uncontrolled DCD programs in place to implement such therapeutic strategies, this call should be extended to the rest of the developed countries as well because all of them would be overlooking strategies proven so effective in saving life with quality–in the authors’ view. Far from being considered an obstacle, existing uncontrolled DCD programs would not be but facilitators of the implementation of NCRP. In fact, they have been applied in selected patients in our country, with the option of DCD being further activated in case of failure–just

as the authors propose.

Of course, Ethical concerns and dilemmas are still to be overcome in DCD, as in other fields of donation and transplantation medicine, but the approach to these dilemmas should start with a detailed study of the facts, based on evidence and not on personal interests or opinions. Uncon- trolled DCD is the result of the coordinated efforts of a huge number of professionals who have made possible to comprise both the interests of the potential organ recipients and those of organ donors, by placing the opportunity of donation as part of end of life care when death occurs–after optimizing all available and appropriate therapeutic options [17]. Under- mining and defaming these important achievements with articles as this one is what threatens the professional and the public perception of organ donation, and this is not precisely

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