# Effects of a novel acetaminophen analog on cardiorespiratory compensatory responses and survival in a male rat model of traumatic hemorrhage

## TL;DR

A new version of acetaminophen called D-112 does not harm survival or blood pressure in rats with traumatic blood loss, suggesting it could be a safe painkiller in such cases.

## Contribution

The study introduces D-112, a novel acetaminophen analog, and evaluates its safety in a traumatic hemorrhage model.

## Key findings

- D-112 did not significantly affect survival times or survival curves in rats with traumatic hemorrhage.
- D-112 transiently increased minute ventilation but did not alter mean arterial pressure.
- D-112 appears to be a safe analgesic option in traumatic hemorrhage scenarios.

## Abstract

When pain is associated with traumatic hemorrhage, medics must be concerned about secondary effects of analgesics on cardiorespiratory systems. A novel analog of acetaminophen, D‐112, was developed to circumvent liver toxicity and improve analgesic efficacy. D‐112 causes dose‐related inhibition of formalin‐induced licking. The objective of this study was to test the effects of D‐112 on survival and cardiorespiratory variables following hemorrhage and extremity trauma (ET). We hypothesized that D‐112 would significantly change cardiorespiratory responses to HEM and thereby decrease survival. Male rats received either vehicle (lactated Ringer's) or D‐112 (50 mg/kg) after conscious hemorrhage of either 37% (n = 10, vehicle and D‐112) or 50% (n = 8, vehicle; n = 11, D‐112) of blood volume following ET, which consisted of soft tissue injury and fibula fracture. Rats were observed for 4 h after the start of hemorrhage. Neither survival times (37% hemorrhage: p = 0.474; 50% hemorrhage: p = 0.306) nor survival curves (37% hemorrhage: p = 0.146; 50% hemorrhage: p = 0.280) differed between treatments. Mean arterial pressure did not differ between treatments (37% hemorrhage: p = 0.742; 50% hemorrhage: p = 0.521). D‐112 transiently elevated minute ventilation (p < 0.001) after both hemorrhages. D‐112 does not alter cardiorespiratory responses to the point of depressing survival, suggesting that D‐112 could be an appropriate analgesic following traumatic hemorrhage.