Effect of Sedation on Pain Perception

Abstract

Background Sedation or anesthesia is used to facilitate many cases of an estimated 45 million diagnostic and therapeutic medical procedures in the United States. Preclinical studies have called attention to the possibility that sedative hypnotic drugs can increase pain perception but it remains unclear whether this observation holds true in humans and whether pain-modulating effects are agent specific or characteristic of intravenous sedation in general. Methods To study this important clinical question, we recruited 86 healthy volunteers and randomly assigned them to receive one of three sedative drugs; midazolam, propofol or dexmedetomidine. We asked participants to rate their pain in response to four experimental pain tasks (cold, heat, ischemic or electrical pain) before and during moderate sedation. Results Midazolam increased cold, heat and electrical pain perception significantly (10-point pain rating scale change = 0.82 ± 0.29, mean ± SEM). Propofol reduced ischemic pain and dexmedetomidine reduced both cold and ischemic pain significantly (−1.58 ± 0.28, mean ± SEM). We observed a gender-by-race interaction for dexmedetomidine. In addition to these drug specific effects, we observed gender effects on pain perception; females rated identical experimental pain stimuli higher than males. We also noted racedrug interaction effects for dexmedetomidine with higher doses of drug needed to sedate Caucasians when compared to African-Americans. Conclusions The results of our study call attention to the fact that intravenous sedatives may increase pain perception. The effect of sedation on pain perception is agent and pain type specific. Knowledge of these effects provides a rational basis for analgesia and sedation to facilitate medical procedures.

Dexmedetomidine versus Midazolam in Procedural Sedation. A Systematic Review of Efficacy and Safety

“…In 2 of the 12 publications the subjects were human volunteers, not patients. One study investigated hemodynamic changes during sedation with dexmedetomidine or midazolam (or propofol) [5], the other evaluated the effects of these sedatives on the perception of various painful stimuli [6]. A priori power analysis was mentioned in 4 of the 12 studies.…”

“…Of the 12 included studies, 4 were given a final JADAD score of 2 or lower [5,6,12,15] (Table 2). Although all 12 studies were randomized, not all were double-blind trials.…”

“…Although all 12 studies were randomized, not all were double-blind trials. Two were volunteer studies in which the authors did not use blinding as this was deemed not feasible or not appropriate [5,6]. The three other studies without double-blinding were from Demiraran et al, Hashiguchi et al and Liao et al [10,12,14].…”

Unrecognized suffering in the ICU: addressing dyspnea in mechanically ventilated patients

“…These include lowering sedation [6], preserving spontaneous breathing activity [7], and the use of low tidal volumes [8] even in the absence of severe lung disorders [9–11]. It cannot be ruled out that sedation may give a falsely reassuring outward appearance of comfort in patients actually suffering from undiminished, or even increased respiratory discomfort, as in the case of pain [12, 13]. For example, pain ratings and pain-related cortical activations in response to cutaneous pain stimuli were increased by moderate propofol sedation.…”

Sedative premedication before surgery – A multicentre randomized study versus placebo

“…Benzodiazepines in general are not devoid of side effects: increased pain perception after surgery [15][16][17], a doubled risk of postoperative delirium, when used in premedication [18]. Hence, our results encourage reconsideration of the use of premedication and possibly limiting these drawbacks.…”