Analgesic Low-Dose Ketamine Infusions and Central Nervous System Adverse Effects: A Prospective Cohort Study

Low dose ketamine infusions (LDKI) may provide adequate adjuvant analgesia while reducing postoperative opioid consumption in specific populations, such as patients with opioid tolerance or high intensity postoperative pain. However, there is currently limited data on the incidence of central nervous system adverse effects such as delirium, hallucinations, agitation, sedation, or nightmares using LDKI in treating postoperative pain.

We aimed to compare the incidence of central nervous system adverse effects in patients receiving an LDKI compared with patients not receiving an LDKI for the first postoperative 48 hours.

Unicentric prospective cohort comparative study.

An academic university hospital.

Patients older than 18 who underwent major orthopedic, abdominal, or thoracic surgery were grouped into those who received an LDKI (LDKI group, n = 101), and patients who did not receive ketamine (non-K group, n = 138) based on the responsible anesthesiologist decision. The LDKI group received a 0.1 mg/kg/h ketamine infusion as part of a multimodal analgesic plan. The primary outcome was a composite of postoperative LDKI-related central nervous system adverse effects (delirium, hallucinations, or nightmares) within the first 48 hours after exposure compared with the non-K group. The secondary outcomes were pain intensity and cardiovascular variables (blood pressure and heart rate).

There were no differences in cognitive dysfunction (delirium), agitation or sedation between groups (P > 0.05). The primary composite objective of central nervous system symptoms occurred in 12.9% of the LDKI group compared with 2.2% in the non-K group. The adjusted risk of psychomimetic symptoms using propensity score matching was an odds ratio of 4.84 (95% CI, 1.33 - 17.76) with a P value < 0.016. The cumulative incidence of nightmares (8.9% vs 0.72%, P = 0.001) and hallucinations (6.8% vs 2.2%, P = 0.071) were both higher in the LDKI group.Hemodynamic variables were not statistically different between groups. Pain level was significantly lower in the LDKI group (P = 0.03), however, both groups presented a mean Visual Analog Scale score below 4 mm.

Our study is limited by its observational method, since no intervention was assigned by the investigator.

An LDKI (0.1 mg/kg/h) for postoperative pain is associated with a low incidence of minor central nervous system effects, i.e., nightmares and hallucinations. There is no significant association with major central nervous system adverse effects, such as delirium, sedation, or agitation, supporting its safety as an adjuvant in multimodal analgesia.