Dr. Carmichael raises pertinent points. There was no evidence that the patient had attempted to induce abortion by any means other than the ingestion of pennyroyal extract and black cohosh root. On physical examination, the patient's uterus was about 4 cm in size and was firm, with a closed os. No blood was present. No abnormalities of the cervix or vagina were noted. On autopsy, the uterine corpus was slightly enlarged and its mucosa was hemorrhagic; the ovaries were slightly enlarged and otherwise unremarkable. The patient had received intravenous Unasyn (ampicillin and sulbactam), gentamicin, and clindamycin on an empirical basis. All blood cultures obtained before and after initiation of antibiotic therapy were negative. Peritoneal cultures, done after the first dose of gentamicin, were also negative except for rare coagulase-negative Staphylococcus and propionibacterium. The latter represent skin contaminants, not pathogens.

Pending autopsy, the discharge diagnoses of the primary physician included bleeding tubal pregnancy, hemorrhagic shock, cardiopulmonary arrest, and brain death. A neurosurgical consultant's opinion, obtained before death, was ectopic pregnancy complicated by intra-abdominal hemorrhage, sepsis, disseminated intravascular coagulation, and cardiopulmonary arrest resulting from the use of pennyroyal and black cohosh. The medical examiner's final ascertainment of cause of death was multiorgan failure and anoxic encephalopathy caused by the ingestion of pennyroyal and black cohosh root.

The results of Western blotting provide a high degree of certainty that the patient's liver proteins were modified by menthofuran metabolites, inasmuch as the antiserum used is selective for the structure of menthofuran metabolites attached to proteins. Therefore, it is very unlikely that septic shock alone could result in the Western blots observed. We agree that the patterns of proteins detected in vitro versus those detected in vivo are not identical. However, several of the same proteins are apparently detected, and differences can be related to the rather long times with which proteins are exposed to reactive metabolites in vivo compared with in vitro. As we noted, the blood and plasma concentrations of menthofuran were low at autopsy. However, because there are no data in humans on the kinetics of pennyroyal constituents and their metabolites, no way is available to attach clinical significance to the concentrations.

The patient may have had complications from both her long-term and short-term ingestion of pennyroyal. As we noted [1, 2], pennyroyal causes gastrointestinal upset, spontaneous abortion, seizures, coma, disseminated intravascular coagulation, hepatic and renal injury, and death. The long-term ingestion may have caused hemorrhage of the patient's ectopic pregnancy. We believe that the more likely reason is that the short-term ingestion of pennyroyal extract was causally related to her presentation, given the onset of symptoms occurring soon after the final ingestion. Moreover, the abrupt increase in her liver enzyme levels from normal baseline levels is consistent with the time course of pennyroyal toxicity. As we acknowledged, however, this could also have reflected a contribution of shock directly or indirectly related to the patient's toxic syndrome. Unfortunately, the cause of death in drug and toxin overdoses is often due to secondary complications of the poisoning rather than the effects on the direct-target organ.