Pupillary reflex dilation in response to incremental nociceptive stimuli in patients receiving intravenous ketamine

Abstract

Pupillometry is a non-invasive monitoring technique, which allows dynamic pupillary diameter measurement by an infrared camera. Pupillary diameter increases in response to nociceptive stimuli. In patients anesthetized with propofol or volatile agents, the magnitude of this pupillary dilation is related to the intensity of the stimulus. Pupillary response to nociceptive stimuli has never been studied under ketamine anesthesia. Our objective was to describe pupillary reflex dilation after calibrated tetanic stimulations in patients receiving intravenous ketamine. After written consent, 24 patients of our pediatric burn care unit were included. They received an oral morphine premedication (0.3 mg kg) 1 h before their scheduled daily dressing change. Just before the procedure, they received 1 mg kg of intravenous ketamine. Two minutes after this bolus, tetanic stimulations of incremental intensities were performed on the arm of each patient (5-10-20-30-40-60 mA, 60 s interval between stimulations). Pupillary diameter, heart rate and movements were recorded before and after each stimulation. Tetanic stimulations were associated with changes in pupillary diameter and heart rate. The magnitude of these changes was significantly influenced by the intensity of stimulation (ANOVA for repeated measures, p < 0.001). Movement was associated with a 32% increase in diameter (ROC curves, AUC 0.758) with 65% sensitivity and 77% specificity. In children, pupillary reflex dilation to nociceptive stimuli persists under deep sedation obtained with 1 mg kg of intravenous ketamine combined with a 0.3 mg kg oral morphine premedication, and its magnitude depends on the intensity of the stimulation. Our results confirm that pupillometry could be a relevant way to monitor nociception in anaesthetised subjects, including those receiving ketamine. Trial registration clinicaltrials.gov, NCT 02648412.

Diagnostic Capability of Pupillary Dilation Reflex to Measure Pain In The Critical Analgosedated Patient

“…Aissou et al [33], working with a group of 100 conscious patients during the immediate postoperative period, obtained a PDR cut-off point of 23% with sensitivity, speci city, PPV and NPV greater than 90%. Sabourdin et al [40] observed a PDR higher than 32% in a group of surgical patients who showed behavioural changes after continuous nociceptive stimulation between 5 and 60 mA. This cut-off point obtained an AUC of 0.758 and a sensitivity and speci city of 0.65 and 0.77, respectively.…”

Evaluation of Nociception during Pediatric Surgery: A Topical Review

“…A PRD amplitude above 32% showed a 65% sensitivity and 77% specificity for movement response to nociception. In children aged 3–12 years, PRD-guided analgesia (PRD between 5–30%) was associated with a 25% decrease in remifentanil consumption compared to blood pressure-guided analgesia (defined as changes of ±20% from the baseline) [ 51 ]. In a study on children aged 1–16 years in which an increased heart rate by 10% was used as marker of nociception, a pupillary diameter cut-off value of 4.2 mm showed a sensitivity of 58% and specificity of 79% [ 42 ].…”

“…Pupillometry-guided anesthesia (target PRD < 30%) was associate with a 48% decrease in postoperative opioid requirements in adults [ 71 ]. In children, patients undergoing pupillometry-based anesthesia showed similar pain score than the conventional group, which however was <3/10 in both groups [ 51 ].…”

Future of paediatric sedation: towards a unified goal of improving practice

“…ketamine (1 mg kg À1 ) in combination with oral morphine (0.3 mg kg À1 ), pupillary reflex dilation persisted in response to nociceptive (and increasing) stimuli. 58…”