Multiple organ transplantation after suicide by acetaminophen and gunshot wound.
ABSTRACT Emergency physicians (EP) and medical toxicologists are integral in identifying and treating patients with overdoses. Transplant centers are expanding acceptance criteria to consider those with poison-related deaths. We present a case of a simultaneous gunshot wound to the head and an acetaminophen overdose. This case highlights the importance of EPs and medical toxicologists in recognizing the medical complexity of suicides, optimizing treatment, and timing of organ procurement. Early antidote administration and aggressive supportive care allowed the patient to be evaluated as a potential donor. EPs and medical toxicologists have integral roles in overdose patients as organ donors.
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ABSTRACT: The treatment of poisoned patients is still largely defined by history, clinical assessment and interpretation of ancillary investigations. Measurement of drug concentrations is clinically important for relatively few compounds. Most measurements form an adjunct to and should not be considered a substitute for clinical assessment. Drug concentrations are particularly important for those compounds where the concentration is predictive of serious toxicity in an otherwise asymptomatic patient.British Journal of Clinical Pharmacology 02/2001; 52 Suppl 1:97S-102S. · 3.58 Impact Factor
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ABSTRACT: Six hundred sixty-two consecutive patients with acetaminophen overdoses were evaluated. Those at risk on the basis of their acetaminophen blood levels, as plotted on the study nomogram, were treated with oral acetylcysteine. Statistically significant differences in severity of hepatic toxicity were observed between patients treated within 16 hours after ingestion and those treated between 16 and 24 hours after ingestion. No deaths occurred among patients treated within 24 hours of ingestion, except for one patient who was an alleged gunshot homicide. Seven percent of patients with plasma acetaminophen levels in the potentially toxic range and treated with acetylcysteine within ten hours of ingestion showed transient SGOT level elevations, whereas 29% of those treated between ten and 16 hours after ingestion and 62% of those treated between 16 and 24 hours after ingestion showed such transient toxicity. No consistent difference in hepatotoxicity could be demonstrated between those patients with a history of chronic alcohol use and those patients with no history of chronic alcohol use. Acute alcohol use resulted in less severe toxic reactions than in those patients without acute alcohol use.Archives of Internal Medicine 03/1981; 141(3 Spec No):380-5. · 11.46 Impact Factor
Volume XI, no. 5 : December 2010 506 Western Journal of Emergency Medicine
Multiple Organ Transplantation after Suicide by
Acetaminophen and Gunshot Wound
Mark E. Sutter, MD*
Michael F. Daily, MD†
Kelly P. Owen, MD*
G. Patrick Daubert, MD*
Timothy E. Albertson, MD, PhD‡
* University of California, Davis, Department of Emergency Medicine, Davis, CA
† University of California, Davis, Department of Surgery, Davis, CA
‡ University of California, Davis, Department of Medicine, Davis, CA
Supervising Section Editor: Brandon K. Wills, DO, MS
Submission history: Submitted March 26, 2010; Accepted May 10, 2010
Reprints available through open access at http://escholarship.org/uc/uciem_westjem
Emergency physicians (EP) and medical toxicologists are integral in identifying and treating
patients with overdoses. Transplant centers are expanding acceptance criteria to consider those
with poison-related deaths. We present a case of a simultaneous gunshot wound to the head and
an acetaminophen overdose. This case highlights the importance of EPs and medical toxicologists
in recognizing the medical complexity of suicides, optimizing treatment, and timing of organ
procurement. Early antidote administration and aggressive supportive care allowed the patient to
be evaluated as a potential donor. EPs and medical toxicologists have integral roles in overdose
patients as organ donors. [West J Emerg Med. 2010; 11(5):506-509.]
Emergency physicians (EP) often play important roles in
the initial stabilization of patients who later become organ
donors. They also play vital roles in the transplantation
process through recognition of potential drug overdoses. As
the list of patients awaiting transplantation grows, acceptance
criteria by transplant centers have expanded to consider those
who have died due to drug intoxication.1,2 Between 2004 and
2008, the Organ Procurement and Transplantation Network
classified drug intoxication as cause of death in approximately
3% of all donors.3 (Table 1).
While the vast majority of drug intoxications manifest
symptoms within the first few hours, delayed or “silent toxins”
exist. The classic examples of poisonings with delayed
manifestations include mushroom poisoning from the Amanita
sp. and acetaminophen. Both are hepatotoxins that may not
produce symptoms for the first 12-24 hours and usually do not
manifest life- or organ-threatening toxicity until 72-96 hours
after the ingestion.4
Delays in toxicity must be considered when evaluating an
overdose patient as a potential transplant donor.
Acetaminophen-induced organ injury is known to cause renal
Table 1. Summary of organ donors classified as drug intoxication compared to all donors (2004-2008)
20042005 2006 2007 2008
** Based on Organ Procurement and Transplantation Network Data as of May 27, 2009
Western Journal of Emergency Medicine 507 Volume XI, no. 5 : December 2010
failure with or without evidence of hepatotoxicity, further
complicating the evaluation of such donors.5-8
We describe the case of a 17-year-old male with a
simultaneous gunshot wound to the head in association
with an acetaminophen overdose. This case demonstrates
the importance of considering the complex medical issue of
suicide and optimizing patient care with supportive care and
early antidote administration.
A 17-year-old male with no significant past medical
history was brought to the emergency department (ED) after a
self-inflicted gunshot wound to the head. In the ED the mother
was specifically asked about potential overdoses. She stated
that there was a recently purchased bottle of acetaminophen in
the garage where her son had been working. She had asked
him to bring her the bottle; approximately five minutes later,
he went into another room and she heard a gunshot.
Upon arrival in the ED, the patient was intubated without
medication. He had a systolic blood pressure of 130mm Hg, a
pulse of 111 beats per minute, a respiratory rate of 16 via
bag-assisted respirations and a temperature of 36.5°C.
Physical exam was notable for a single penetrating wound to
the right temporal bone. Pupils were fixed and dilated. There
was no evidence of trauma anywhere else on his body. The
computed tomography scan of his brain demonstrated a
non-survivable head injury with multiple skull fractures,
intraparenchymal, intraventricular, subarachnoid and subdural
blood. Additionally, there was significant cerebral edema with
evidence of tonsillar herniation. The remainder of the physical
exam was consistent with brain death, with no additional signs
of trauma. Initial laboratories returned with a hemoglobin, 11
gm/dL; platelets, 218 103/mm3; sodium, 138 mEq/L;
potassium, 2.9 mEq/L; chloride, 104 mEq/L; bicarbonate, 22
mEq/L; blood urea nitrogen, 12 mg/dL; and creatinine, 0.96
mg/dL. His aspartate transaminase (AST) was mildly elevated
at 50 IU/L and his alanine transferase was normal at 20 IU/L.
Initial international normalized ratio was 1.26. His
acetaminophen level drawn at arrival was markedly elevated
at 134 mg/L. The EPs initiated N-acetylcysteine (NAC)
therapy and requested a medical toxicology consultation.
Family expressed their interest in organ and tissue donation.
The intensive care service requested input from the toxicology
team with regard to immediate treatment for the patient, as
well as timing and toxicological issues that could affect organ
donation and transplantation.
After conversations with the family, there was no further
history available regarding potential ingestions or time of
ingestion. An exact time of ingestion could not be determined.
The family located the bottle and found approximately 20
grams of acetaminophen missing, an amount capable of
producing fulminant hepatic failure. Given the lack of
overdose information with evidence of a significant ingestion,
intravenous NAC was continued indefinitely. Charcoal
therapy was considered, but with the unknown time of
ingestion and the duration of time elapsed from pre-hospital
transportation through ED resuscitation, the patient was
outside the window for likely therapeutic benefit.
The process of brain death evaluation was initiated. Our
institutional policy for pediatric patients (defined as <18 years
of age) is to have two separate brain death exams on separate
calendar days. During this period, a multidisciplinary group of
pediatric intensive care physicians and medical toxicologists
participated in supportive care. Initial plans for heart, lung,
and pancreas donation were decided, but the viability of the
kidneys and liver were unknown. The next 24 hours of
laboratory evaluation is summarized in Table 2.
After the patient was declared brain dead, organs were
recovered and transplanted into six different recipients. The
heart, lung, pancreas and one of the kidneys were successfully
transplanted, and at three months post transplant all organs
were functioning well. The liver was split, with one recipient
also receiving a kidney. The patient who received the right
hemi-liver alone did not experience complications and had
excellent allograft function at three months. The patient who
received both the left hemi-liver and a kidney had a prolonged
intensive care hospitalization for two months post transplant
for infectious complications; however, the transplanted organs
Table 2. Laboratory trends during the process of brain death determination
Laboratory Test 15:52
AST (IU/L)5557 4748Brain
ALT (IU/L) 2017 20 20 192020
INR 1.262.14 1.431.281.28 1.301.31
APAP (mg/L) 13479 4827 1611 <10
T ½ (hours)
4.59 5.17 4.925.08**
** Half lives become less reliable in the terminal portion of the elimination phase, especially as you approach the limit of detection.
AST, aspartate transaminase; ALT, alanine transferase, INR, international normalized ratio; APAP, N-acetyl-p-aminophenol
Acetaminophen Overdose/Gunshot Wound Suicide and Transplant Sutter et al.
Volume XI, no. 5 : December 2010 508 Western Journal of Emergency Medicine
were functioning normally during the intensive care stay and
at three months post transplantation.
This unique case highlights the importance of considering
the complex medical issues related to suicide, recognition of a
potential ingestion and early antidote administration.
Additionally, this case demonstrates many toxicological issues
in both potential donor and transplant recipients. There is
limited data on organ recovery and transplant in donors with
overdoses. The possibility of delayed manifestation of toxicity
becomes more complicated when the immediate cause of
death was not due to the ingestion.
There were no identified contraindications to transplant
the heart, lungs, pancreas, and intestines. Several issues
needed to be addressed regarding the kidneys and liver. One of
these was the timing of organ recovery. No specific criteria
exist for the timing of liver transplantation using a donor with
acetaminophen overdose and elevated AST. While delay in
recovery may be reassuring to the centers accepting the liver
and kidneys, the possibility existed that the traumatic brain
injury itself could trigger many pathologic processes, such as
diffuse intravascular coagulation, which could affect the
viability of the other organs.
Acetaminophen has been known to induce renal
insufficiency in approximately 2% of overdoses.9 There have
been case reports describing kidney donation after
acetaminophen overdose 10. In some of these cases, the donors
had elevated creatinine, and in one case the patient was
oligoanuric for three hours prior to harvesting organs.
However, the cause of death in these cases was liver failure
from acetaminophen overdose. Therefore it is hard to
extrapolate these results to prospectively predict if a kidney
will be viable when the cause of death is unrelated.
Predicting which patients with acetaminophen overdose
will develop renal failure has been difficult to elucidate
beyond general risk factors for hepatic failure. A prospective
study evaluating proteinuria found it was not an early marker
that would progress to renal failure in acetaminophen
overdoses.11 Additionally, the onset of renal failure typically
occurred between day two and day five after the overdose with
peak creatinine levels on day seven.6, 12 This was concerning
given the fact that our patient was declared brain dead on day
two. The majority of case reports demonstrated creatinine that
had returned to baseline within one month, suggesting that
renal failure is likely reversible. 12
While information regarding acetaminophen-induced
renal failure is limited, hepatotoxicity from acetaminophen is
well studied. In significant acetaminophen overdoses,
transaminases typically begin to rise between 18 and 30 hours,
followed by signs of multi-organ involvement typically
manifesting between 72 and 96 hours post-ingestion. 4
Additionally, the initiation of NAC prior to eight hours post
ingestion has been shown to prevent liver failure regardless of
initial acetaminophen level.13 This patient had an unknown
time of ingestion, making it impossible to determine the risk
of hepatotoxicty with his first level of 134 mg/L.
Our literature search returned no published reports of liver
donation after acetaminophen overdose. This is not surprising,
as most patients with acetaminophen overdose either have full
recovery, or death due to complications of hepatic failure.
Given this lack of data, it was unclear at what time liver
donation could be considered safe. Typically, in treatment of
an acetaminophen overdose, therapy with NAC is initiated and
transaminase levels are followed in conjunction with
confirmation that the acetaminophen level becomes
undetectable. However, the timing of the recovery of other
organs prohibited this delay to follow the liver function.
The institutional policy regarding pediatric brain death
provided the opportunity to check serial acetaminophen levels
prior to declaring the patient brain dead. The half-lives listed
in Table 2 range from 4.59 to 5.17 hours. As oxidative damage
to the liver occurs, the ability to eliminate the drug decreases
and thus prolongs the calculated half-life. Two previous
studies evaluating acetaminophen half-life determinations to
predict toxicity have found that half-lives less than 2.5 hours
and 3 hours respectively make toxicity unlikely.14,15 Studies
have also shown that half-lives of greater than four hours put
the patient at increased risk of hepatotoxicity and demonstrate
the longer the half-life, the higher the rate of hepatotoxicity. 16,
17 Typically, the use of acetaminophen half-lives to predict
toxicity is not recommended due to lack of specificity and
multiple confounders such as ongoing gastrointestinal
absorption, or co-ingestions. Given the half-lives of this
patient were greater than four hours, transplantation of the
liver was considered high risk.
The patient’s transaminases failed to change over the 24
hours of observation prior to the declaration of brain death.
Besides the possibility that not enough time had elapsed to see
the transaminases rise, two additional explanations are
possible. First, given our lack of knowledge regarding the time
of ingestion, the initial level of 134 mg/L could have been less
than a four- hour level and reflected significant continued
absorption. With serial levels decreasing, this would make his
ingestion low probability for hepatotoxicity. The second
explanation for his lack of hepatotoxicity may be the result of
the early initiation of NAC stopping hepatotoxicity from
In summary, early recognition of a potential overdose
and NAC administration in the ED optimized the patient as a
potential donor. The use of overdose patients as organ donors
may serve as an increasing source of organs to meet the
growing needs of patients awaiting transplant. It is vital that
EPs and medical toxicologists play integral roles in overdose
patients as organ donors.
Sutter et al. Acetaminophen Overdose/Gunshot Wound Suicide and Transplant
Western Journal of Emergency Medicine 509 Volume XI, no. 5 : December 2010
We would like to thank Golden State Donor Services for
their effort and contribution to this manuscript.
Address for Correspondence: Mark Sutter, MD, Department of
Emergency Medicine, University of California, Davis 2315 Stock-
ton Blvd, Sacramento CA, 95817. Email: mark.sutter@ucdmc.
Conflicts of Interest: By the WestJEM article submission agree-
ment, all authors are required to disclose all affiliations, funding
sources and financial or management relationships that could
be perceived as potential sources of bias. The authors disclosed
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Acetaminophen Overdose/Gunshot Wound Suicide and Transplant Sutter et al.