Pupillometric Monitoring of Nociception in Cardiac Anesthesia

Abstract

Background: High-dose opioids are conventionally used for cardiac anesthesia, but without monitoring of nociception. In non-cardiac surgical procedures the intra - operative dose of opioids can be individualized and reduced with pupillometric monitoring of the pupillary pain index (PPI; scale 1-9). A randomized controlled trial was carried out to explore whether pupillometry can be used for nociception monitoring in cardiac anesthesia and whether it leads to opioid reduction.

Methods: A sample of 57 cardiac surgery patients receiving continuously administered sufentanil (initial dosage 0.7 μg*kg-¹*h-¹) was divided into a PPI group (sufentanil reduction if PPI<3 up to a minimum of 0.15 μg*kg-¹*h-¹, n=32) and a control group (standard anesthesia; n = 25). The primary outcome was the time from the end of anesthesia to extubation. The secondary outcomes were total intraoperative dose of sufentanil/noradrenaline, postoperative pain intensity (numeric rating scale [NRS] 0-10) and intraoperative awareness. German Clinical Trials Registry no. DRKS 00012329.

Results: The primary outcome, extubation time, did not differ between the two groups (1.14 h, 95% confidence interval [-0.99; 3.27], p = 0.592). Compared with the control patients (68% male, age 70 ± 10.4 years, PPI 1.1 ± 0.2), the mean sufentanil infusion rate in the PPI patients (81% male, age 68 ± 10.3 years, PPI 1.1 ± 0.2) decreased by 81.8% (-0.68 μg*kg-¹*h-¹ [-0,7; -0.67], p<0.001) to the predetermined minimum level, without intraoperative awareness. Moreover, the noradrenaline dose was reduced by 56% (1235.51 μg [321.91; 2149.12], p = 0.005) and the postoperative pain intensity by 45% (2.11 NRS [0.93; 3.3] after 24 h, p = 0.003).

Conclusion: Pupillometry is appropriate for nociception monitoring in cardiac anesthesia. Thereby a considerable reduction of intraoperative opioids as well as increased intraoperative hemodynamic stability was achieved and postoperative opioid-induced hyperalgesia was prevented. The consistently low PPI scores, indicating adequate analgesia, suggest that further reduction of opioid doses is feasible.

Figure 1

a) Extubation time (h), b) cumulative intraoperative sufentanil, and c) noradrenaline administration (both in µg), as well as d) pain intensity 24 h and 48 h (NRS) after admission to the intensive care unit in the control (blue, n = 25) and PPI group (red, n = 32). Variables are presented as boxplots (i.e., minimum, maximum, median, first quartile, and third quartile) and mean values. N = 57. b) The administration of a sufentanil bolus at the time of skin incision temporarily increased the initial dose to 1.1 ± 0.21 µg*kg^–1*h^–1 (from: 0.81 ± 0.17, p <0.001 [-0.40, -0.18], effect size [ES]: 1.76) in the control group, not in the PPI group (0.66 ± 0.01 µg*kg^–1*h^–1). The first sufentanil reduction occurred early after skin incision in both groups (controls: 18.6 ± 9.0 vs. PPI: 15.9 ± 3.7 min). In the PPI group, the minimum dose was reached in 87.5% of patients (n = 28/32) on average after 70% of the total surgery time. NRS, Numerical Rating Scale; PPI, Pupillary Pain Index group

Figure 2

Time course of BIS, PPI measurements, and sufentanil dose. All variables (presented as mean values ± standard deviations) were measured every 15 min, beginning with the skin incision and ending with the skin suture (mean surgery time 232.4 ± 60.2 min). In the control group (blue, n = 25), 17 patients had a surgery time of at least 180 min and 10 of at least 240 min, whereas in the PPI group (red, n = 32), 23 patient had 180 min and 12 had 240 min. In both groups, sufentanil was administered for induction (0.5 µg*kg^–1 lean body weight) and maintained until skin incision (0.7 µg*kg^–1*h^–1). Beginning with the skin incision, subsequent dosing was at the discretion of the experienced anesthesiologist in the control group; therefore, patients received an additional sufentanil bolus (black arrow), as is traditionally the case, whereas in the PPI group, sufentanil was continuously reduced, beginning with the skin incision and guided by a low PPI, until the minimum sufentanil dose (0.15 µg*kg^–1*h^–1, dotted line) defined in the protocol was reached in the PPI group. N = 57. BIS, Bispectral Index; OP, operation; PPI, Pupillary Pain Index

Figure 3

PPI and BIS measurements in the control (blue dots, n = 25) versus PPI group (red squares, n = 32). BIS, Bispectral Index; PPI, Pupillary Pain Index; N= 57

eFigure 1

Flow diagram on study design and randomization Apfel score, predicts the risk of postoperative nausea and vomiting (– 4); BDI, Beck’s Depression Inventory; BIS, Bispectral Index; CAM-ICU, Confusion Assessment Method for the Intensive Care Unit; ET, extubation time; CPB, cardiopulmonary bypass; Euro-Score II, European System for Cardiac Operative Risk Evaluation; ICU, intensive care unit; NRS, Numerical Rating Scale for pain intensity, PONV, postoperative nausea and vomiting; PPI, Pupillary Pain Index; SES, Schmerzempfindungsskala (German pain perception scale)

eFigure 2

Time course of pupillary variation (%) and pupillary diameter (mm). Both variables, presented as mean values ± standard deviation, were measured every 15 min, between skin incision and suture (mean surgery time 232.4 ± 60.2 min). There were no differences between groups. N = 57, PPI, Pupillary Pain Index group