The effect of perioperative intravenous s-ketamine on acute and chronic postoperative craniotomy pain compared to placebo

Effective treatment of postoperative pain after craniotomy and especially after
temporal lobectomy for drug-resistant epilepsy is a challenge. In daily
practice, acetaminophen is combined with opioids. However, patients still have
moderate to severe pain complaints. Increasing the amount of opioids seems to
have little effect. An alternative, as add-on medication to opioids, could be
s-ketamine. S-ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist
which has been shown to be effective and safe in low-dose in a variety of
studies for treatment of postoperative pain. It reduces both the total opioid
consumption and the postoperative pain scores. Until now, the addition of
s-ketamine to opioids as part of a multimodal approach for postcraniotomy pain
has never been studied.

This study has been transitioned to CTIS with ID 2024-514020-16-00 check the CTIS register for the current data.

To investigate the effectiveness of s-ketamine as add-on medication to a
multimodal pain approach with acetaminophen and opioids compared to placebo
with the same multimodal pain approach on the total postoperative opioid
consumption, the postoperative pain scores registered with the visual analogue
score (VAS) and numeric rating scale (NRS), patient satisfaction, hospital stay
and adverse events.

Prospective, randomized, double blind, placebo-controlled, two-arms, clinical
trial. One arm will receive intravenous s-ketamine as add-on medication to
acetaminophen and opioids, the other arm will receive a placebo (NaCl 0.9%) and
acetaminophen and opioids.

Patients are randomized by computer to receive either a 0.25mg/kg bolus
s-ketamine followed by a continuous infusion of 0.1mg/kg/u s-ketamine or a
placebo infusion (NaCl 0.9%) for 48 hours. The study medication will start
prior to the skin incision.

Anaesthesiologists use s-ketamine as part of their multimodal pain approach in
daily practice. Low-dose s-ketamine is safe to administer and is not associated
with serious side effects or a significant increase of adverse events.
Prior to the operation, all patients will receive questionnaires about
health-related quality of life (RAND-36-item Health Survey [RAND SF-36]),
surgical fear (Surgical Fear Questionnaire [SFQ]), depression (Center for
Epidemiologic Studies Depression scale [CES-D]), pain catastrophizing (Pain
Catastrophizing Scale [PCS]), severity of the patient's pain (Brief Pain
Inventory-Short Form [BPI-SF]), neuropathic pain (Douleur Neuropathique en 4
Questions [DN4]) and a self-compiled questionnaire inquiring the
characteristics of the headache. Postoperatively, as described above, data are
collected (VAS+NRS scores, total amount of analgetics, adverse events).
Furthermore, patients will be asked to fill in a pain (headache) diary at
postoperative day 1-4 and at day 7 and the occurrence of delirium will be
tested in the 7 postoperative days with the Delirium Observation Screening
(DOS) scale. At day 7, a final pain (headache) assessment will be taken. A
follow up questionnaire will be sent to each operated patient after 3 and 6
months to evaluate the course of chronic post-craniotomy pain (headache).