Ketamine May Enhance Recovery Following Surgery

Ketamine may improve the quality of recovery (QoR) in patients undergoing thoracoscopic, i.e., chest, surgery when given around the time of procedure (perioperatively). 

Recently published results from a clinical trial conducted at a university hospital suggest that perioperative administration of “S”-ketamine enhanced the quality of recovery in patients who underwent video-assisted thoracic surgery (VATS), including improvements in depression and pain levels experienced after surgery.  VATS is common surgery used in the treatment of many lung and heart diseases including lung cancer (arising in approximately 6.3% of Americans during their lifetime) and pacemaker placement in those with an abnormal heart beat pattern (affecting approximately 25-30% of those with heart failure).

Researchers conducting the clinical study used the extensively validated and widely administered “QoR-40” scale to assess the postoperative quality of recovery in patients by measuring levels of comfort (e.g., clarity of thought, satisfaction with anesthetic, and ability to undertake daily living activities), emotions (e.g., depression and anxiety), physical independence (e.g., ability to stand, walk, eat, and dress), pain, and cognitive ability (e.g., word generation and recall) following surgery.  

The overall QoR-40 score at 48 hours following surgery was higher in the patient group that had been given S-ketamine compared with those who had only received a placebo (saline).  Patients who received S-ketamine reported lower pain scores at rest and coughing at 24- and 48-hours following surgery than those who had received saline treatment.  Additionally, those in the S-ketamine group required less opioid pain relief for breakthrough pain following the procedure than those who had been given placebo. 

Researchers used the “Hospital Anxiety and Depression Scale Depression Subscale” (HADS-D) score to assess for depressive symptoms following surgery.  Compared with the placebo group, S-ketamine significantly reduced depression scores at 48 hours after surgery.

S-ketamine, also known as esketamine, has been used in the approved medical treatment of conditions including depression and as an anesthetic including for the induction of anesthesia for patients who are at very high-risk for deadly anesthesia-related complications.  In March 2019, the U.S. Food and Drug Administration (FDA) approved esketamine for the treatment of depression in adults and one year later, did so again for the short-term treatment of suicidal thoughts.

Ketamine has been studied extensively as an adjunct for perioperative pain-relief, with statistically significant reports of improved pain scores and reduction in postoperative opioid consumption for a broad range of surgical procedures.  Previous evidence has suggested that ketamine may also be useful in patients with opioid tolerance and for preventing chronic postsurgical pain.  In a 2011 systemic review of 70 studies where intravenous (IV) ketamine was used for perioperative pain relief, analysis determined that ketamine had reduced opioid use in patients most significantly in those who underwent upper abdominal and thoracic procedures.  The review also suggested ketamine to have a greater pain-relieving effect in operations that were considered more painful, with less opioid use also reported for patients who had undergone painful procedures.  

Though a body of evidence has suggested ketamine to be useful for surgical patients on chronic opioid therapy and for preventing persistent postsurgical pain, great caution should be given when considering its administration to patients with kidney or liver failure, as the metabolism of ketamine may exacerbate conditions of this nature.  Although ketamine proved more effective than placebo in post-surgery pain and symptom relief in the most recent study covering its usage in such settings, previous studies have suggested perioperative ketamine administration to have an approximately twice greater likelihood of causing psychomimetic effects, e.g., hallucinations, out-of-body sensations, vivid dreams, and dysphoria (a general state or feeling of uneasiness or unhappiness), than in those patients who had been given placebo.  Low doses of ketamine have also been suggested to cause reactivation of psychosis in schizophrenic patients, though a history of psychosis is still not considered an explicit criterion for exclusion for clinical studies assessing the effects of ketamine in postoperative and therapeutic settings.  Other side effects of pain-relieving (sub-anesthetic) doses of ketamine following surgical procedures include fleeting increases in blood pressure and heart rate.  Though most side effects are relatively inconsequential, a risk-benefit assessment should be conducted in all cases where a patient may be averse to receiving sub-anesthetic ketamine (e.g., elevated eye or head pressure, uncontrolled high blood pressure, history of psychosis, liver dysfunction, and more).