The incidence of myocardial ischemia following ketamine administration is unknown. Ketamine is included in the American Heart Association (AHA) list of medications that may cause or exacerbate heart failure and has been reported to precipitate myocardial ischemia in the elderly 2,3. There is limited evidence of ketamine precipitating myocardial ischemia during short-term use in the emergency department (ED). The cardiovascular stimulation-inhibition balance of ketamine may be altered by severe critical illness, and the doses of any induction agent should be significantly reduced in critically ill patients. It is a drug of choice for short-term procedures when muscle relaxation is not required.33 The effect of ketamine on the respiratory and circulatory systems is different from that of other anesthetics.
Ketamine Induced Acute Systolic Heart Failure
All sedations had a nurse present for the sedation and a physician responsible for monitoring the patient separate from the procedural physician. All patients received continuous monitoring of blood pressure, heart rate, oxygen saturation, and end-tidal CO2. Prospectively, a convenience sample of patients older than 50 years receiving ketamine for procedural sedation in the ED was used. Recruitment occurred during hours when the three-person research team members were working clinically in the ED. Patients were offered enrollment after sedation choice was made by the treating provider, and informed consent was obtained if patients agreed to enrollment.
We present 2 critically ill patients who experienced cardiac arrest following the administration of ketamine for rapid sequence intubation (RSI). The literature regarding the use of etomidate and ketamine for RSI in critically ill patients is reviewed and options for sedation during endotracheal intubation in this population are discussed. In a 2012 case report by Dewhirst et al. 4, two critically ill patients suffered from cardiovascular arrest following ketamine administration for rapid sequence intubation.
Mechanism of action
A similar case report to ours showed that upon administration of intravenous (IV) ketamine, a patient experienced delusions, tachycardia, hypertension, and 1 mm ST depression in V3–V6 on ECG with elevated troponins. Cardiac catheterization showed no significant coronary artery disease, and the echocardiogram showed a left ventricular EF of 45% with moderate apical hypokinesis which improved to 60% the following day14. In this ketamine-induced model of cardiac toxicity, the PARP–AIF/NF-κB pathways may contribute to structural remodelling, while β-NGF may play an important role in sympathetic remodelling. Metoprolol was effective in preventing the ketamine-induced cardiac toxicity in our experiments.
She denied any family history of cardiac diseases and never experienced similar symptoms previously. Physical examination showed basal crackles on lung auscultation and 2+ bilateral lower extremity oedema. She had a troponin level of 0.07 ng/ml and a B-type natriuretic peptide (BNP) level of 2511 pg/ml. Electrocardiogram was normal sinus rhythm (Fig. 1) and transthoracic echocardiography (TTE) showed left ventricular ejection fraction (EF) of 15%, dilated left ventricle, and severe tricuspid and mitral regurgitation (Fig. 2 and Fig. 3).
- Ketamine is an agent commonly used in emergency department procedural sedations due to its anesthetic and analgesic properties and respectable safety profile.
- The epicardium in the ketamine plus metoprolol-treated animals showed no obvious grey and rough areas.
- The patient was controlled under mechanical ventilation for 24 hours with synchronised intermittent mandatory ventilation mode pressure support then weaned gradually and extubated on the third postoperative day.
- She reported using ketamine twice weekly along with smoking half a pack of cigarettes daily.
In our case, the patient had elevated troponins along with an EF of 15% which improved in 2–4 weeks. The transient nature of acute systolic heart failure along with ruling out other possible etiologies leaves ketamine-induced heart failure as the most plausible explanation. The data on the management of ketamine induced heart failure is sparse and is mainly driven by similar case reports. Close follow-up and monitoring are required, and steps should be taken to ensure cessation of ketamine use.
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The sympathomimetic effect of ketamine can produce elevations in blood pressure, heart rate, and cardiac output, which are typically mild-to-moderate. Ketamine increases coronary perfusion, enhancing myocardial contraction and increasing myocardial oxygen consumption. Hence, ketamine should also be used with caution in patients with cardiac disease, especially coronary artery disease (e.g., angina). Ketamine raises pulmonary arterial pressures somewhat more than systemic pressures and may exacerbate preexisting pulmonary hypertension or congestive heart failure. In addition, cardiac monitoring may be prudent in patients with thyroid disease requiring thyroid replacement therapy.
Ketamine & cardiovascular stability
Ketamine is 2-(0-Chlorophenyl)-2-(methylamino)-cyclo-hexanone hydrochloride, a phencyclidine derivative that was introduced in 1965. It differs from other intravenous anesthetics in many respects, and produces dissociative anesthesia rather than generalised depression of the central nervous system. Ketamine has bronchodilating effects, and protective airway reflexes are preserved to some extent.
- These reactions lasted for 1–3 min after injection, and full recovery required 15–25 min.
- Ketamine can produce nystagmus with pupillary dilation, salivation, lacrimation, and spontaneous limb movements with increased muscle tone through indirect sympathomimetic activity.
- NF-κB is a family of inducible transcription factors that plays an anti-apoptotic role in cell cycling by regulating the expression of genes involved in apoptosis and cell proliferation.
- The transient nature of acute systolic heart failure along with ruling out other possible etiologies leaves ketamine-induced heart failure as the most plausible explanation.
- The literature regarding the use of etomidate and ketamine for RSI in critically ill patients is reviewed and options for sedation during endotracheal intubation in this population are discussed.
- Screening for ketamine use disorders should be considered in patients presenting with acute systolic heart failure.
What are the cardiovascular effects of Ketamine?
The patient was discharged on GDMT and a follow-up echocardiogram showed an improvement in EF to 50%. Intubation was difficult to perform due to laryngospasm, and the endotracheal tube was stuck on the vocal cords but finally inserted and resuscitation was successful. The patient was controlled under mechanical ventilation for 24 hours with synchronised intermittent mandatory ventilation mode pressure support then weaned gradually and extubated on the third postoperative day. She recovered well and was transferred to the Surgical Ward where she completed her recovery and was subsequently discharged a week later without further complications.
Secondary outcomes included changes in vital signs after ketamine administration and a case-control analysis comparison of patients with changes suggestive of ischemia to those without. Clinically significant vital sign change was defined as an increase or decrease of greater than or equal to 20% from baseline. Growing evidence suggests that long-term abuse of ketamine does harm the heart and increases the risk of sudden death. The present study was performed to explore the cardiotoxicity of ketamine and the protective effects of metoprolol.
The cardiovascular stimulation-inhibition balance of ketamine may be altered by severe critical illness, and doses of any induction agent should be significantly reduced in critically ill patients. In our case, we suspect catecholamine is depleted as our patient suffered from major stress and that could have been worsened by the rapid bolus which was given and the body failed to compensate. In isolated rabbit and canine hearts and in intact dogs, ketamine has been demonstrated to produce myocardial depression 7. At lower, sub-anesthetic doses, it is used as a treatment for pain and treatment-resistant depression. Metoprolol prevented the cardiotoxicity of ketamine, indicating a promising new therapeutic strategy.
Heart failure in young adults is uncommon and known etiologies include familial cardiomyopathy, peripartum cardiomyopathy, and tachycardia-induced cardiomyopathy. Less frequently heart failure can be seen in spontaneous coronary artery dissection, malignant hypertension, or illicit drug use such as cocaine use disorder8. We report a case of acute systolic heart failure likely secondary to street ketamine use disorder. In the ischemia group, the median dose was higher than the milligram per kilogram dosing of the non-ischemia group (0.84 vs. 0.56).
In fact, I very rarely see a drop in blood pressure when I use it for RSI even in significantly shocked patients. One should however try to remain open to evidence that disconfirms ones biases, lest we allow science to be replaced by religion. I therefore was interested to read a report of two cases does ketamine cause cardiac arrest of cardiac arrest following the administration of ketamine for rapid sequence intubation (RSI)(1).