Answers to a Journalist Researching Matthew Perry's Death

A journalist contacted me recently and asked me these questions:

1.     Can ketamine by itself cause respiratory depression?

From the anesthesia book, Miller is considered the Bible of anesthesia. Ketamine produces doses related to unconsciousness and analgesia. This is termed dissociative anesthesia because patients who receive ketamine alone appear to be in a cataleptic state.

Ketamine’s effects on the respiratory system are minimal, and it has actually been found to increase respiratory drive at relative doses. However, a transient one-to-three-minute decrease in ventilation after a bolus that would be used in intraoperative general anesthesia can occur.

It would take unusually high doses to produce apnea, and again, given the levels found in his system, this is very unlikely.

2.     What do you believe is the most likely route of ketamine ingestion, and could it be possible that the coroners may have missed the skin puncture from a ketamine injection?

This is a great question. I think it should be prefaced with Matthew Perry, who was an experienced drug addict. Such individuals can accomplish acts of drug administration that seem, at times, beyond comprehension. The question of whether the coroners may have missed a skin puncture is possible. For example, if a tiny insulin needle was used to administer some amount of ketamine intramuscularly. It’s highly doubtful that the coronary would miss an intravenous line puncture. Thus, Mr. Perrys route of administration could have included oral, intramuscular, and intranasal. However, it would have been an intentional administration of ketamine to produce the levels found in his body. This again brings up the question of how his levels got that high without an intravenous administration.

3. Would Perry still be awake enough to walk down to the hot tub if he self-administered an anesthesia dose of 3270-3540 ng/ml? Is it possible for someone to build enough tolerance to ketamine to do so?

The answer is yes. He could have built up enough tolerance to ketamine to have such an effect. Since no drug paraphernalia was found around the site of the jacuzzi, it can only be assumed that he self-administered or had help with the administration elsewhere from his assistants or doctors. Since we know the ketamine entered his body, however, there were no syringes, oral ketamine, or nasal ketamine found during the investigation. This brings up the likelihood that somebody collected those items and disposed of them before the investigation occurred.

4. Do you think Perry may have been using ketamine recreationally?

At first, I didn’t know the answer to this question. It is well known he had been receiving legitimate ketamine treatments for some years. In recent articles, it has been suggested that he received ketamine every day. This is unfortunate as it suggests he was highly addicted.

5. I noticed that drug interactions between ketamine + buprenorphine and lorazepam + buprenorphine can both lead to respiratory depression. To what extent could these interactions have contributed to Perry’s death?

It’s difficult to say for sure how these drug interactions affected Mr. Perry. In theory, they certainly could have contributed. However, the drug toxicology reports suggest that he was taking these drugs as prescribed, and we can safely assume he has been on these drugs for long periods. It’s reasonable to suggest that he had taken this combination of drugs in the past, given his history of ketamine treatments, benzodiazepine use, and suboxone use. Again, this is all speculation but just logical thinking.

6. Your substack post seemed to suggest that Perry likely died from a heart attack. Can you confirm your thoughts on what may have happened, considering the information from the coroner’s report?

He was certainly a setup for a heart attack. He had pre-existing coronary artery disease (CAD) in the left anterior descending (LAD) artery, COPD, was mildly obese, had just finished 2 hours of high-intensity exercise, had ketamine in his system, etc.  Even though there was no evidence of ischemia in the autopsy, he easily could have suffered a lethal arrhythmia. Below is a reference below from BMC. At the end of the day, we will never know the answer to this question.

Conclusion of study:

“In a referred cohort of SUD cases, unspecific cardiac findings were seen in 63% of the autopsied with the most common findings including hypertrophy/enlargement of heart, coronary artery atheromatosis and diffuse fibrosis. These unspecific findings may be precursors or early signs of underlying structural cardiac disorders but could also be spur findings in patients with inherited arrhythmogenic disorders. In total, 37% of all victims had no cardiac finding on autopsy.”

Yazdanfard, P.D., Christensen, A.H., Tfelt-Hansen, J. et al. Non-diagnostic autopsy findings in sudden unexplained death victims. BMC Cardiovasc Disord 20, 58 (2020). https://doi.org/10.1186/s12872-020-01361-z