Use of ketamine for reversing acute depression in a critically ill pretransplant patient

Abstract

A 68-year-old with a history of ischemic cardiomyopathy, chronic kidney disease, hypertension, and anxiety was admitted to the intensive care unit (ICU) in cardiogenic shock. After an intubation and several days in the ICU, he expressed hopelessness with further care and was considering a transition to hospice. The treatment team was concerned that clinical depression was influencing his decision. After obtaining consent, depression was treated with 0.5 mg/kg of intravenous ketamine for 3 days, with rapid and significant improvement in his mood. He made an informed choice to pursue a workup for heart transplantation. Besides improving his mood, ketamine led to vivid subjective experiences. This case provides a qualitative account of the patient's experience. It raises crucial questions about the influence of depressive symptoms in decision-making in critically ill patients and the potential role of ketamine in the rapid resolution of depressive symptoms and subsequent changes in care decisions.

Medical decision-making in critically ill patients is often challenging, particularly when patients face severe illness and high-stakes treatment decisions¹. Patients with major depression may have difficulty registering, retaining, and processing information, making it challenging to make informed decisions about their care. Depression can lead to hopelessness. These feelings can make it difficult for patients to objectively consider the potential benefits and drawbacks of different treatment options and weigh them in a way that aligns with their values and goals. Depression can also lead to fatigue and poor motivation, making it difficult for patients to make decisions.

In critically ill patients, these complex, often life-and-death decisions must be made quickly. It is important to recognize and rapidly address any underlying conditions contributing to diminished decision-making capacity. Ketamine has shown great promise in the rapid resolution of depressive symptoms, although evidence about its use in critically ill patients is limited.2, 3, 4

Ketamine is a dissociative anesthetic with a unique pharmacological profile, including N-methyl-D-aspartate receptor antagonism and modulation of glutamatergic neurotransmission. It has a plasma half-life of 2.5 hours and a distribution half-life of 7 to 11 minutes. Ketamine has been used in intensive care units (ICUs) for decades to provide analgesia, sedation, and bronchodilation without impacting hemodynamic stability.⁵ Ketamine has also been used as a drug of abuse in the recreational setting for its dissociative and euphoric effects. In this setting, ketamine has various nicknames including K, special K, and super-acid. Ketamine has garnered evidence as a rapid-acting antidepressant agent, well tolerated, and is known to be hemodynamically stable.6, 7 Several randomized-controlled trials have reported that subanesthetic doses of ketamine produce significant and rapid improvement in depressive symptoms in individuals with treatment-resistant depression. One small retrospective study has shown promise for use in ICU patients with depressive symptoms⁸; however, none of these patients were part of the transplant population.

This case report highlights the impact of depressive symptoms on decision making, rapid resolution of depressive symptoms with ketamine, and subsequent restoration of decision-making that aligned with long-standing values.

Case summary

A 68-year-old male with a history of ischemic cardiomyopathy, chronic kidney disease, hypertension, and anxiety was admitted to the ICU in cardiogenic shock after placement of drug-eluting stent placement in the left anterior descending artery. At the time, he was New York Heart Association class 3, American Heart Association stage D, and Stevenson group C. He required inotropic support with an intravenous dobutamine drip and vasopressor support with an intravenous vasopressin drip. On ICU day number 3, he met with the palliative team and was unsure if he wanted to pursue additional aggressive measures and expressed interest in pursuing palliative care. He acknowledged feeling depressed, and the palliative team's extensive discussion with the patient and his wife raised concerns that depressive symptoms influenced his capacity to make medical decisions. Ketamine was offered as a treatment for depressive symptoms.

After obtaining consent, depression was treated with 0.5 mg/kg of intravenous ketamine for 3 days, with rapid and significant improvement in his mood. The day following the third infusion, he made an informed choice to pursue a workup for heart transplantation. The team waited until the next day to ensure that more than 5 plasma half-lives had passed and that all the acute euphoric effects of the ketamine infusion had completely resolved. Besides improving his mood, ketamine led to vivid subjective experiences. The patient was interviewed on day 11 after his first ketamine infusion and his qualitative interview regarding his experience can be found in Table 1. He underwent Impella 5.5 (Abiomed, Danvers, Massachusetts, United States of America) placement via the axillary artery on ICU day 22. He underwent combined heart and kidney transplantation on ICU day 45. He was discharged home on postoperative day 19 after his heart and kidney transplant.

Table 1.

Patient’s experience on ketamine

Expectations	“I looked forward to it because I knew once I’d come out (of the ketamine), I would be laughing and having fun with my family.”
Dissociative experience	“I could hear the nurses in the background. And I could still hear real voices and those around the world shut. So the real world is done, and you are in this place where I’m like, ok, here we go, and let me ride this out."
Effect on hopelessness	"Then I heard my sons talking. I remember as I was coming out, but not quite crystal clear, yet I heard my sons talking and having their banter together, which was a reason to stay. Keep going, stay.”
Effect on mood	“I mean, I had a much better week the week after.”
Advocacy	“I would tell them (other patients) if they are down and depressed 1 or 2 days after an operation like me, I would tell them to give it a try but to be prepared. If they aren’t spiritual or whatever things they pull from, to get to a positive place before they go. I believe they will have a whole better experience if they do that.”

Direct quotes from the patient from an audio interview done with the patient 11 days after the first ketamine dose.

Discussion

Major depression is common in critically ill patients. It is easy to overlook because somatic symptoms of major depression overlap with physical illness, and emotional distress might be considered an expected response to hospitalization for serious health problems. Mood, somatic, and cognitive symptoms of major depression can significantly impact medical decision-making capacity. Traditional psychopharmacological treatments take 4 to 6 weeks to be effective, and there is a risk of significant adverse effects and drug-drug interactions, especially in critically ill patients.

Ketamine has traditionally been used in the ICU to provide sedation and analgesia. More recently, it has shown success in treatment-resistant depression. Antidepressant response to ketamine is often rapid and can potentially help ICU patients with depressive symptoms, mitigating the effects of depressive symptoms on the capacity to make medical decisions. This case raises crucial questions about the influence of depressive symptoms in decision-making in critically ill patients and the potential role of ketamine in the rapid resolution of depressive symptoms and subsequent changes in care decisions. When using ketamine in this context, it is important to wait enough time before reviewing decisions or goals of care to ensure that all of ketamine's euphoric and dissociative effects have completely resolved.

A small retrospective case series of ICU patients showed improved mood and better sleep with ketamine.⁸ This case report further illustrates the profound and immediate effect that ketamine can have on an ICU patient's mood and motivation. Additionally, the patient's testimony shows that while dissociative symptoms can be the side effects of ketamine, these last for a short duration, are impacted by expectations, and are not necessarily viewed as adverse effects by the patient.

This case report highlights the need for heightened awareness to screen and manage depression in critically ill patients. Depression in the first-year post-transplant is associated with worse outcomes in the heart transplantation patient population.⁹ Current tools for detecting major depression in this critically ill patient population might be insufficient given the length of time to see a clinical improvement. Additional studies are needed for more robust screening and diagnostic tools and randomized-controlled trials for treating major depression in this patient population with ketamine.

Disclosure statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. None for authors Dr Shapiro, Dr Chauhaun, and Dr Sanghavi. Dr Martin serves on the Scientific Advisory Board of Attgeno AB, with all compensation to Mayo Clinic. He also serves on the Data Safety Monitoring Board for the GLUSorb Trial (NCT05526950), with all compensation to Mayo Clinic.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.