Propranolol attenuates hemorrhage and accelerates wound healing in severely burned adults

Abstract

Introduction: Propranolol, a nonselective β-blocker, exerts an indirect effect on the vasculature by leaving α-adrenergic receptors unopposed, resulting in peripheral vasoconstriction. We have previously shown that propranolol diminishes peripheral blood following burn injury by increasing vascular resistance. The purpose of this study was to investigate whether wound healing and perioperative hemodynamics are affected by propranolol administration in severely burned adults.

Methods: Sixty-nine adult patients with burns covering ≥ 30% of the total body surface area (TBSA) were enrolled in this IRB-approved study. Patients received standard burn care with (n = 35) or without (control, n = 34) propranolol. Propranolol was administered within 48 hours of burns and given throughout hospital discharge to decrease heart rate by approximately 20% from admission levels. Wound healing was determined by comparing the time between grafting procedures. Blood loss was determined by comparing pre- and postoperative hematocrit while factoring in operative graft area. Data were collected between first admission and first discharge.

Results: Demographics, burn size, and mortality were comparable in the control and propranolol groups. Patients in the propranolol group received an average propranolol dose of 3.3 ± 3.0 mg/kg/day. Daily average heart rate over the first 30 days was significantly lower in the propranolol group (P < 0.05). The average number of days between skin grafting procedures was also lower in propranolol patients (10 ± 5 days) than in control patients (17 ± 12 days; P = 0.02), indicative of a faster donor site healing time in the propranolol group. Packed red blood cell infusion was similar between groups (control 5.3 ± 5.4 units vs. propranolol 4.4 ± 3.1 units, P = 0.89). Propranolol was associated with a 5 to 7% improvement in perioperative hematocrit during grafting procedures of 4,000 to 16,000 cm(2) compared to control (P = 0.002).

Conclusions: Administration of propranolol during the acute hospitalization period diminishes blood loss during skin grafting procedures and markedly improves wound healing in severely burned adults. As burn patients require serial surgical interventions for motor and cosmetic repair, restricting blood loss during operative intervention is optimal.

Figure 1

Proposed mechanism by which propranolol induces peripheral vasoconstriction. Induction of peripheral vasoconstriction by propranolol can be attributed to three main actions. (1) Inhibition of β₁ receptors in the heart decreases cardiac output, thereby inducing reflexive peripheral vasoconstriction via stimulation of α₁ receptors in vascular smooth muscle. (2) Direct inhibition of β₂ receptors incites peripheral vasoconstriction. (3) By blocking β-adrenergic effects of circulating catecholamines epinephrine and norepinephrine, α₁-adrenergic receptor effects remain unopposed, resulting in vascular smooth muscle contraction. Solid arrows indicate direct effects, and broken arrows indicate indirect effects.

Figure 2

Patient enrollment diagram.

Figure 3

Patient enrollment and timeline of hospital course. Patients were admitted within 7 days of burn injury. Over the next 48 hours, patients were randomized to control (n = 34) or propranolol (n = 35) groups and then underwent total burn wound excision. Thereafter, patients underwent serial skin grafting procedures once donor sites wounds healed. Patients were then discharged once wounds were deemed to be 95% healed.

Figure 4

Daily heart rate. Daily mean heart rate was significantly lower in patients on propranolol than in control patients. Data are presented as mean ± standard error of the mean. ^* P <0.05.

Figure 5

Propranolol significantly stabilizes perioperative hematocrit levels. Patients receiving propranolol maintained perioperative hematocrit levels compared to control patients. Propranolol was associated with a 1.6% improvement in perioperative hematocrit levels during grafting procedures with a graft area of 100 cm², 2.5% improvement with 300 cm², 3.6% improvement with 1,000 cm², 5.2% improvement with 4,000 cm², and 7.1% improvement with 16,000 cm² (P = 0.002). Data are presented as adjusted mean ± 95% confidence intervals (shaded).