Background & Aims

Low-Dose Ketamine Infusion (LDKI) is effective as adjuvant analgesia in postoperative pain (POP) to opioids (1, 2). Patients administered LDKIs have lower pain scores and reduce opioid consumption by up to 40% (3). Psychomimetic symptoms are the most common adverse effects associated with ketamine and are dose-dependent (4). Delirium and hallucinations are observed with the highest frequency in previous studies using ketamine in POP analgesia and may impair patient recovery. LDKI is a growing alternative for adjuvant analgesia, especially in a group of patients with opioid tolerance or hyperalgesia risk (1). Description of psychomimetic effects in LDKI studies is limited to spontaneous reports in most trials. The aim of this study was to investigate the psychomimetic effects of LDKI with validated scales in a prospective controlled study.

Methods

Prospective, cohort study in a sample of 239 POP patients treated with multimodal analgesia including opioids. Per institutional acute pain protocol, the case anesthesiologist may indicate LDKI based on clinical criteria. Two groups were analyzed, the first group (group LDKI) was treated with ketamine infusion (0.1 mg/kg/h) and the second group (control) received standard analgesia without ketamine. Psychomimetic symptoms were assessed 24-48 hours postoperatively. Delirium was measured using the Confusion Assessment Method (CAM) score, agitation-sedation using Richmond Agitation-Sedation Scale (RASS), presence of hallucinations with the Launay-Slade Hallucination Scale-Revised, and appearance of nightmares through directed questions. The level of pain was measured with the Visual Analog Scale (VAS). Hemodynamic variables, including Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR), were also measured.

Results

101 patients received LDKI and 138 standard analgesia. The cumulative frequency of delirium was 1.98%, hallucinations 6.9%, nightmares 8.9%, sedation and agitation 1.9% in the LDKI group; versus 0.72%, 2.2%, 0.72% and 1.5%, respectively, in the standard care group (figure 1). We observed a statistically significant increase in the occurrence of nightmares in the LDKI group (P<0.001), no statistical differences were observed for the other studied variables. The risk of experiencing psychomimetic symptoms was 12.8%, with and odds ratio (OR) of 4.84 (95% CI: 1.33–17.7; P=0.016). The mean VAS score at 48 hours was 1.83 (SD 1.36) in the LDKI group, compared to 2.89 (SD 1.87) in the control group. No significant differences were observed in hemodynamic variables between LDKI treatment and standard care.

Conclusions

LDKI as an adjuvant to opioids in postoperative analgesia is not associated with major psychomimetic effects, such as delirium, hallucinations, sedation, or agitation. A statistically significant difference was observed in the occurrence of nightmares. However, this frequency does not seem to compromise recovery in POP patients. Pain level was adequate in both groups. This finding suggests that LDKI is a safe alternative to treat POP patients experiencing high pain intensity levels to decrease opioid consumption (5) or in patients chronically exposed to opioids at risk of tolerance/hyperalgesia.

References

1. Schwenk ES, Viscusi ER, Buvanendran A, Hurley RW, Wasan AD, Narouze S, Bhatia A, Davis FN, Hooten WM, Cohen SP. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018 Jul;43(5):456-466. doi: 10.1097/AAP.0000000000000806. PMID: 29870457; PMCID: PMC6023582.
2. Schauer SG, Naylor JF, Davis WT, Borgman MA, April MD. An analysis of prolonged, continuous ketamine infusions. Mil Med 2022; 187:e547-e553.
3. De Kock M, Lavand’homme P, Waterloos H. “Balanced analgesia” in the perioperative period: Is there a place for ketamine? Pain. 2001;92(3):373–80.
4. Brinck ECV, Tiippana E, Heesen M, Bell RF, Straube S, Moore RA, et al. Perioperative intravenous ketamine for acute postoperative pain in adults. Cochrane Database Syst Rev. 2018;2018(12).
5. Loftus RW, Yeager MP, Clark JA, Brown JR, Abdu WA, Sengupta DK, Beach ML. Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology. 2010 Sep;113(3):639-46. doi: 10.1097/ALN.0b013e3181e90914. PMID: 20693876.

Presenting Author

Esteban Calle

Poster Authors

Adriana Cadavid-Calle

Professor

University of Antioquia and Hospital Universitario San Vicente Foundation

Lead Author

Julio Camelo

Universidad de Antioquia

Lead Author

Fabian Casas

universidad de antioquia

Lead Author

Cristian Ramirez

Universidad de Antioquia

Lead Author

Luisa Aguirre

Universidad de Antioquia

Lead Author

Esteban Calle

Research Group Young Investigator Hospital San Vicente

Lead Author

Julio Ernesto Camelo Rincon

Lead Author

Topics

  • Treatment/Management: Pharmacology: Adverse effects