Adverse drug reactions during S-ketamine infusion in patients with chronic pain: 5 years of experience.

Background and aims
S-ketamine has been used for over a decade to treat several chronic pain syndromes such as Complex Regional Pain Syndrome. There is limited information on the occurrence of adverse drug reactions of S-ketamine infusions at subanesthetic doses. The aim of present study was to evaluate adverse drug reactions (ADR) in a cohort of patients receiving S-ketamine for chronic pain.

Methods
In this retrospective observational study, patients receiving S-ketamine infusions for chronic pain from January 2012 to December 2017 at the University Medical Centre Utrecht were included.  S-ketamine was administered in a daycare setting starting with a 5 mg bolus, followed by a gradual dose increase from 5 to 30 mg/hour during five hours on average. Patient characteristics, ADR and reasons for premature ending of protocol were collected from medical charts. 

Results
During the 5-year period, 201 included patients received 511 S-ketamine infusions (range 1-20 infusions per patient) with a mean dose of 104.3 mg (range 20-200 mg). In 93% of the first S-ketamine administrations ADR were reported including dizziness (40.3%), somnolence (30.3%), nausea (28.4%), vomitus 14.4%, hallucinations (tactile 18,9%, visual 17.9%, emotional 10.0%) and urine retention resulting in catheterization (10%). Premature ending of protocol based on side effects was recorded during first infusion (25.4%) and subsequent infusions (5.8%). 

Conclusions
Adverse drug reactions during S-ketamine infusion for chronic pain are common. Physicians should be highly alert on these reactions, inform patients about these reactions prior to treatment and consider (preemptive) administration of anti-emetic drugs, benzodiazepines and/or α2-agonists.

ADVERSE DRUG REACTIONS DURING S-KETAMINE INFUSION IN PATIENTS WITH CHRONIC PAIN: 5 YEARS OF EXPERIENCE