The Use of Ketamine for Air Medical Rapid Sequence Intubation Was Not Associated With a Decrease in Hypotension or Cardiopulmonary Arrest.

OBJECTIVE: Rapid sequence intubation (RSI) is associated with a number of complications that can increase morbidity and mortality. Among RSI agents used to blunt awareness of the procedure and produce amnesia, ketamine is unique in its classification as a dissociative agent rather than a central nervous system depressant. Thus, ketamine should have a lower risk of peri-RSI hypotension because of the minimal sympatholysis compared with other agents. Recent recommendations include the use of ketamine for RSI in hemodynamically unstable patients. The main goal of this analysis was to explore the incidence of hypotension and/or cardiopulmonary arrest in patients receiving ketamine, etomidate, midazolam, and fentanyl during air medical RSI. We hypothesized that ketamine would be associated with a lower risk of hemodynamic complications, particularly after adjusting for covariables reflecting patient acuity. In addition, we anticipated that an increased prevalence of ketamine use would be associated with a decreased incidence of peri-RSI hypotension and/or arrest. METHODS: This was a retrospective, observational study using a large air medical airway database. A waiver of informed consent was granted by our institutional review board. Descriptive statistics were used to present demographic and clinical data. The incidence rates of hypotension and cardiopulmonary arrest were calculated for each sedative/dissociative agent. Multivariable logistic regression was used to calculate the odds ratios of both hypotension and arrest for each of the sedative/dissociative agents. The prevalence of use for each agent and the incidence of hemodynamic complications (hypotension and arrest) were determined over time. RESULTS: A total of 7,466 RSI patients were included in this analysis. The use of ketamine increased over the duration of the study. Ketamine was associated with a higher incidence of both hypotension and arrest compared with other agents, even after adjustment for multiple covariables. The overall incidence of hypotension, desaturation, and cardiopulmonary arrest did not change over the study period. CONCLUSIONS: Although the incidence of hemodynamic complications was higher in patients receiving ketamine, this may reflect a selection bias toward more hemodynamically unstable patients in the ketamine cohort. The incidence of hypotension and arrest did not change over time despite an increase in the prevalence of ketamine use for air medical RSI. These data do not support a safer hemodynamic profile for ketamine.

Schwann cell LRP1 regulates remak bundle ultrastructure and axonal interactions to prevent neuropathic pain.

Trophic support and myelination of axons by Schwann cells in the PNS are essential for normal nerve function. Herein, we show that deletion of the LDL receptor-related protein-1 (LRP1) gene in Schwann cells (scLRP1(-/-)) induces abnormalities in axon myelination and in ensheathment of axons by nonmyelinating Schwann cells in Remak bundles. These anatomical changes in the PNS were associated with mechanical allodynia, even in the absence of nerve injury. In response to crush injury, sciatic nerves in scLRP1(-/-) mice showed accelerated degeneration and Schwann cell death. Remyelinated axons were evident 20 d after crush injury in control mice, yet were largely absent in scLRP1(-/-) mice. In the partial nerve ligation model, scLRP1(-/-) mice demonstrated significantly increased and sustained mechanical allodynia and loss of motor function. Evidence for central sensitization in pain processing included increased p38MAPK activation and activation of microglia in the spinal cord. These studies identify LRP1 as an essential mediator of normal Schwann cell-axonal interactions and as a pivotal regulator of the Schwann cell response to PNS injury in vivo. Mice in which LRP1 is deficient in Schwann cells represent a model for studying how abnormalities in Schwann cell physiology may facilitate and sustain chronic pain.