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BRIEF COMMUNICATIONS: Clinical Transplantation

Successful transplantation of donor organs from a hemlock poisoning victim

Foster, Preston F.1 4; McFadden, Robert1; Trevino, Raul1; Galliardt, Scott1; Kopczewski, Lea Ann1; Gugliuzza, Kristene2; Gonzalez, Zulma3; Wright, Francis1

Author Information
doi: 10.1097/01.TP.0000079828.82128.E9

Abstract

Despite the improving results after organ transplantation, more patients with a variety of end-stage organ failures are dying while awaiting transplantation. Because of this critical situation, many transplant programs have resorted to using so-called “marginal donors” (i.e., donors not previously thought to be usable). Sources of marginal donor organs are victims of poisoning, including those involving carbon monoxide, tricyclic antidepressants, methanol, and cyanide (1). The following case report describes the donor evaluation and recipient outcomes of a somewhat uncommon donor with brain death secondary to poison hemlock ingestion.

CASE REPORTS

The donor was a 14-year-old previously healthy white female who was hiking with a friend in a wooded central Texas area on a weekend nature outing. Both hikers became hungry and decided to ingest plants that were growing in the area. Both developed symptoms within 1 hour of ingestion, and these were initially attributed to “allergies.” The other person had ingested a smaller amount of the plant, and her symptoms remained limited to nausea, tingling of the lips and extremities, and malaise. The eventual donor had similar initial symptoms, which progressed to loss of consciousness and apnea. Emergency medical personnel found the donor in respiratory arrest and bradycardia. An endotracheal tube was placed, and the patient became asystolic and subsequently underwent chest compressions for 20 minutes with return of cardiac function. The donor was given intravenous fluids and vasopressor agents and was transported by helicopter to a trauma center.

After arrival at the hospital, plant samples provided by the companion were identified as hemlock (Conium maculatum). The patient was treated with gastric lavage and activated charcoal administration. She remained comatose, and a computed tomography scan of the head showed severe cerebral edema. Brain death was pronounced at approximately 36 hr after ingestion of hemlock.

Consent was obtained from the family for multiple organ donation. The case required medical examiner referral, and the examiner required that one entire kidney and 50 g of liver tissue be retained for forensic purposes. The donor developed pulmonary edema and hypoxia, which precluded lung donation, with arterial blood gases showing a po2 66 mm Hg, pCO2 34 mm Hg, and pH 7.40 on a tidal volume of 10 mL/kg body weight, oxygen of 100%, and ventilator rate 14 per minute with positive end-expiratory pressure of 7 cm H2O. Decreased cardiac function was believed to be a result of the initial arrest episode and precluded heart donation. An echocardiogram showed an ejection fraction of 33% to 39% with a shortening fraction of 16% to 19%.

Prerecovery laboratory tests were essentially normal (Table 1). Blood, urine, and tracheal cultures were negative. All required serologic tests were negative (hepatitis A, B, and C, human immunodeficiency virus, rapid plasma reagin, and cytomegalovirus). Epstein-Barr serology was positive.

Table 1
Table 1:
Preprocurement laboratory tests

The abdominal organ procurement was performed with standard multiorgan retrieval technique (2) using cold perfusion with University of Wisconsin solution and local ice slush cooling. There were no hypotensive periods during recovery, and pressor support was provided with dopamine at 11 mg/kg body weight per minute. There was a moderate amount of fluid present on opening the abdomen that was negative on Gram stain and later culture incubation. There were no other unusual intraoperative findings. Frozen section biopsy of the liver showed no significant abnormalities and 5% macrosteatosis. Kidney biopsy showed no abnormality. Using a stapling device, a section of the left lateral segment of the liver was removed and sent along with the right kidney to the medical examiner as required for forensic study.

According to reports from the medical examiner’s office, autopsy findings showed neuropathologic findings consistent with anoxic brain injury. There was marked inflammation of spinal nerves. Gas chromatographic/mass spectroscopic examination of donor serum and tissue (renal and liver samples) removed for forensic testing at the time of procurement were negative for coniine (2-propylpiperdine). Identical testing of the plant material obtained at the scene of the intoxication was positive for coniine.

Recipient Outcomes

The three respective recipients of the liver, kidney, and pancreas all had immediate graft function and no signs of transmission of toxic alkaloids. All are doing well with satisfactory transplant function at more than 180 days after transplantation.

The liver recipient was a 62-year-old woman with cirrhosis caused by hepatitis C. She underwent transplantation after a cold ischemia time of 3.75 hr. Immediate bile production was noted. The patient was extubated 18 hr after transplantation. Initial posttransplantation tests showed a total bilirubin of 0.4 mg/dL, alkaline phosphatase of 137 IU/L, aspartate aminotransferase of 202 IU/L, alanine aminotransferase of 121 IU/L, and an international normalized ratio of 1.3. Immunosuppression was accomplished with daclizimab, tacrolimus, mycophenolate, and steroids. This patient was discharged on the 11th hospital day. There have been no subsequent complications or rejection episodes.

The pancreas recipient was a 30-year-old male who had a prior kidney transplant with normal allograft function. The procedure was completed with a cold ischemia time of 14 hr. No insulin was required after transplantation up to this date. Posttransplantation tests revealed an amylase of 90 IU/dL and lipase of 71 IU/dL. This patient was discharged on the seventh day after transplantation. There have been no subsequent complications.

The kidney recipient was a 12-year-old girl with end-stage renal disease caused by immune complex nephritis. She underwent transplantation with a cold ischemia time of 21 hr. The kidney functioned immediately, and the patient was discharged on the eighth day with a serum creatinine level of 1.3 mg/mL. There have been no complications.

DISCUSSION

Hemlock (C. maculatum) is a member of the Umbelliferae family of rhyzomal plants, which includes parsnip and wild carrot (3). The plant was introduced into the United States from Europe as an ornamental plant and is now endemic nationwide. It has a fern-like leaf, tuberous root, and grows 3 to 9 feet tall (3). The plant contains a group of coniine (2-propylpiperdine) alkaloid analogues that are toxic and are distributed in all the plant tissues (4). The principal toxin is gamma-coniceine, which has a median lethal dose of 12 mg/kg body weight in mice (5). The total alkaloid content can be up to 2.5% of the dry weight of plant material (6). The alkaloids are metabolized in liver and muscle tissue, and the half-life of the agents at lethal doses is not known. Single doses of coniine have been noted to leave residual levels of 100 to 200 parts per million in liver tissue up to 7 days after dose in animal models (7).

Hemlock alkaloid action was examined in animal models and found to inhibit spinal cord reflexes and depress autonomic activity and, in large doses, to cause neuromuscular blockade (5). This action may lead to respiratory depression and anoxic brain injury with death within 24 hr of ingestion. No direct toxic effects have been described regarding liver or kidneys, although rhabdomyolysis and associated acute renal failure have been reported in conjunction with hemlock poisoning (8). There is no antidote, and treatment consists of supportive care including sedation, intubation, and ventilation (8). Survivors often have not shown permanent sequelae and have not been reported as exhibiting long-term liver or kidney damage. Nonsurvivors often proceed to brain death without serious extraneural damage, thereby making them possible multiorgan donors.

It should be noted that water hemlock (Cicuta virosa) is a different yet related toxic plant that may be more lethal than poison hemlock (C. maculatum). Water hemlock produces a C(17) polyacetylene neurotoxin termed cicutotoxin, which produces direct brain-neural injury through the induction of convulsions (9). Water hemlock is not involved in this report.

The major concerns in this case were as follows: (1) the direct effect of the toxin on the organs for transplant, (2) the possibility of transmission of toxin with the transplanted organ, and (3) the forensic issues involving the medical examiner. These concerns had to be addressed rapidly to arrive at a decision regarding organ utilization. An Internet search of the literature and consultation with colleagues in pharmacology and toxicology were useful and predicted minimal direct or preservation-related injury to indexed procured organs. Available information indicated there should be no effect on organ function and that any transmission of the agent would be minimal and transient, although there had been cases of transmission to humans of toxin by ingested waterfowl that were intoxicated with poison hemlock (10). The medical examiner required the retention of one kidney and 50 g of liver tissue. It would seem that smaller amounts of tissue would be suitable for forensic purposes, with detection reported in as little as 5 g of liver tissue (11).

CONCLUSIONS

Anoxic death from hemlock (C. maculatum) ingestion is not a contraindication to use of organs for transplantation. There was no effect on organ function and no evidence of transmission of toxin in this case. Forensic considerations should be able to be satisfied without prohibiting donation or withholding transplantable organs. Water hemlock (C. virosa) was not involved in this incident and should not be confused with the findings regarding C. maculatum in this report.

This report may lead to consideration of donation in the case of other victims of poisoning and provides confirmation of the safety and efficacy of donation for poison hemlock victims. Hopefully this will help in a small way with the organ donor scarcity that leads to many patient deaths each year.

Acknowledgment.

The authors thank Wilburn F. Foster, Jr., for assistance in the editing of this manuscript. The authors also thank Dr. Gary Kunsman, Ph.D., of the Bexar County Medical Examiner’s Office in San Antonio, TX, for the development of the toxicologic assay for the determination of coniine levels in the plant material and donor blood and tissue.

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