Background Ketamine is currently recommended for analgesic use on the battlefield for Soldiers with severe hemorrhage and compromised respiration. However, few controlled studies have been conducted to support such use. Hence, we conducted the following study to determine effects of an intravascular analgesic dose of ketamine on respiratory responses to trauma and a 55 % hemorrhage (T+Hem) in conscious rats. We hypothesized that ketamine would have no adverse effects on respiration under such experimental conditions. Methods Rats were randomly assigned to one of two experimental groups: 1) T + Hem given 0.9% saline (Veh; n=8); or 2) T + Hem given 5 mg/kg ketamine in saline (0.5 mg/100 μl; Ket, n=7). All rats (male; ~ 350grams) were surgically implanted with a carotid catheter. After 24 hours, rats were anesthetized briefly (10 min) to undergo trauma (crushing of the right gastrocnemius and semimembranosus muscles for 30 sec with forceps) and fibula fracture. Rats were allowed to awaken, and 90 min later were placed in a whole body plethysmography chamber. Rats then underwent a conscious hemorrhage (~55% of blood volume during 25 min) via the indwelling carotid catheter. At the end of hemorrhage, Veh or Ket was injected via the carotid catheter. Respiratory measures were collected over 1 min intervals and analyzed via Data Sciences International FinePointe software. Primary respiratory measures were respiration rate (RR; breaths/min), tidal volume (TV; ml), and minute volume (MV; ml/min; RR x TV). TV and MV were normalized by body weight. To further characterize respiration, components of the respiratory cycle were evaluated: Inspiratory time (Ti, sec), time spent inhaling during in each breath; Expiratory time (Te; sec), time spent exhaling during each breath); Peak inspiratory flow (Pif, ml/sec), estimated maximum inspiratory flow that occurs in one breath; Mean inspiratory flow (Mif, equal to VT/Ti; ml/sec); Peak expiratory flow (Pef, ml/sec), estimated maximum expiratory flow that occurs in one breath. Rats were observed for 75 min after injection. Data were analyzed via multiway analysis of variance (ANOVA) for repeated measures using the Statistical Analysis System. Results After injection, Veh was associated with gradually declining (P <.05) levels of RR, MV, Pif, Pef, and Mif. Te gradually increased (P ≤ 0.045) after Veh, whereas TV and Ti were stable during the ensuring 75 min period. Compared with Veh: 1) Ket had no effects on RR, TV, Ti, Te, and Mif; and 2) Ket transiently and modestly (P≤ 0.046) decreased MV, Pif, and Pef at specific time points after injection. Conclusions Our results suggest that the Ket-associated decreases in MV resulted primarily from decreased Pif and Pef. It is extremely important that pain medications administered on the battlefield not depress respiration responses during hemorrhage. In our animal model of trauma and hemorrhage, a loss of 55% blood volume produced significant respiratory depression; however, Ket did not meaningfully exacerbate these responses. These results support the use of Ket in wounded Soldiers with severe hemorrhage and compromised respiration.
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