Ketamine Compared With Morphine for Out-of-Hospital Analgesia for Patients With Traumatic Pain: A Randomized Clinical Trial.

Importance: Pain is a common out-of-hospital symptom among patients, and opioids are often prescribed. Research suggests that overprescribing for acute traumatic pain is still prevalent, even when limits restricting opioid prescriptions have been implemented. Ketamine hydrochloride is an alternative to opioids in adults with out-of-hospital traumatic pain. Objective: To assess the noninferiority of intravenous ketamine compared with intravenous morphine sulfate to provide pain relief in adults with out-of-hospital traumatic pain. Design, Setting, and Participants: The Intravenous Subdissociative-Dose Ketamine Versus Morphine for Prehospital Analgesia (KETAMORPH) study was a multicenter, single-blind, noninferiority randomized clinical trial comparing ketamine hydrochloride (20 mg, followed by 10 mg every 5 minutes) with morphine sulfate (2 or 3 mg every 5 minutes) in adult patients with out-of-hospital trauma and a verbal pain score equal to or greater than 5. Enrollment occurred from November 23, 2017, to November 26, 2022, in 11 French out-of-hospital emergency medical units. Interventions: Patients were randomly assigned to ketamine (n = 128) or morphine (n = 123). Main Outcomes and Measures: The primary outcome was the between-group difference in mean change in verbal rating scale pain scores measured from the time before administration of the study drug to 30 minutes later. A noninferiority margin of 1.3 was chosen. Results: A total of 251 patients were randomized (median age, 51 [IQR, 34-69] years; 111 women [44.9%] and 140 men [55.1%] among the 247 with data available) and were included in the intention-to-treat population. The mean pain score change was -3.7 (95% CI, -4.2 to -3.2) in the ketamine group compared with -3.8 (95% CI, -4.2 to -3.4) in the morphine group. The difference in mean pain score change was 0.1 (95% CI, -0.7 to 0.9) points. There were no clinically meaningful differences for vital signs between the 2 groups. The intravenous morphine group had 19 of 113 (16.8% [95% CI, 10.4%-25.0%]) adverse effects reported (most commonly nausea [12 of 113 (10.6%)]) compared with 49 of 120 (40.8% [95% CI, 32.0%-49.6%]) in the ketamine group (most commonly emergence phenomenon [24 of 120 (20.0%)]). No adverse events required intervention. Conclusions and Relevance: In the KETAMORPH study of patients with out-of-hospital traumatic pain, the use of intravenous ketamine compared with morphine showed noninferiority for pain reduction. In the ongoing opioid crisis, ketamine administered alone is an alternative to opioids in adults with out-of-hospital traumatic pain. Trial Registration: ClinicalTrials.gov Identifier: NCT03236805.

Continuous Endogenous Exhaled CO Monitoring by Laser Spectrometer in Human EVLP Before Lung Transplantation.

Endogenous production of carbon monoxide (CO) is affected by inflammatory phenomena and ischemia-reperfusion injury. Precise measurement of exhaled endogenous CO (eCO) is possible thanks to a laser spectrometer (ProCeas® from AP2E company). We assessed eCO levels of human lung grafts during the normothermic Ex-Vivo Lung Perfusion (EVLP). ProCeas® was connected in bypass to the ventilation circuit. The surgical team took the decision to transplant the lungs without knowing eCO values. We compared eCO between accepted and rejected grafts. EVLP parameters and recipient outcomes were also compared with eCO values. Over 7 months, eCO was analyzed in 21 consecutive EVLP grafts. Two pairs of lungs were rejected by the surgical team. In these two cases, there was a tendency for higher eCO values (0.358 ± 0.52 ppm) compared to transplanted lungs (0.240 ± 0.76 ppm). During the EVLP procedure, eCO was correlated with glucose consumption and lactate production. However, there was no association of eCO neither with edema formation nor with the PO2/FiO2 ratio per EVLP. Regarding post-operative data, every patient transplanted with grafts exhaling high eCO levels (>0.235 ppm) during EVLP presented a Primary Graft Dysfunction score of 3 within the 72 h post-transplantation. There was also a tendency for a longer stay in ICU for recipients with grafts exhaling high eCO levels during EVLP. eCO can be continuously monitored during EVLP. It could serve as an additional and early marker in the evaluation of the lung grafts providing relevant information for post-operative resuscitation care.

High inhaled oxygen concentration quadruples exhaled CO in healthy volunteers monitored by a highly sensitive laser spectrometer.

Carbon monoxide (CO) monitoring in human breath is the focus of many investigations as CO could possibly be used as a marker of various diseases. Detecting CO in human breath remains a challenge because low concentrations (

Is intravenously administered, subdissociative-dose KETAmine non-inferior to MORPHine for prehospital analgesia (the KETAMORPH study): study protocol for a randomized controlled trial.

BACKGROUND: Acute pain is a common condition among prehospital patients and prompt management is pivotal. Opioids are the most frequently analgesics used in the prehospital setting. However, opioids are highly addictive, and some patients may develop opioid dependence, even when they are exposed to brief opioid treatments. Therefore, alternative non-opioid analgesia should be developed to manage pain in the prehospital setting. Used at subdissociative doses, ketamine, a noncompetitive N-methyl-D-aspartate and glutamate receptor antagonist, provides analgesic effects accompanied by preservation of protective airway reflexes. In this context, we will carry out a randomized controlled, open-label, multicenter trial to compare a subdissociative dose of ketamine to morphine to provide pain relief in the prehospital setting, in patients with traumatic and non-traumatic pain. METHODS/DESIGN: This will be a multicenter, single-blind, randomized controlled trial. Consecutive adults will be enrolled in the prehospital setting if they experience moderate to severe, acute, non-traumatic and traumatic pain, defined as a numeric rating scale score greater or equal to 5. Patients will be randomized to receive ketamine or morphine by intravenous push. The primary outcome will be the between-group difference in mean change in numeric rating scale pain scores measured from the time before administration of the study medication to 30 min later. DISCUSSION: This upcoming randomized clinical trial was design to assess the efficacy and safety of ketamine, an alternative non-opiate analgesia, to manage non-traumatic and traumatic pain in the prehospital setting. We aim to provide evidence to change prescribing practices to reduce exposition to opioids and the subsequent risk of addiction. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03236805 . Registered on 2 August 2017.

Exhaled carbon monoxide is correlated with ischemia reperfusion injuries during ex vivo lung perfusion in pigs.

Measurement of exhaled carbon monoxide (eCO) might help in the selection of lung grafts during ex vivo lung perfusion (EVLP) since its endogenous production is increased under ischemia reperfusion. The objective of this study was to measure eCO variations depending on the extent of lung ischemia reperfusion injuries. Using a porcine model and a laser spectrometer instrument, eCO was measured during EVLP. eCO was compared after 30 min (D0) or 24 h (D1) of cold ischemia. The ability of eCO to distinguish lungs deemed suitable for transplantation was evaluated. Six lungs were studied at D0 and compared to six lungs studied at D1. eCO was systematically higher on D1 (1.35 ± 0.26 ppmv versus 0.95 ± 0.31 ppmv, p = 0.01). The best threshold concentration for eCO to select lungs was 0.86 ppmv (area under the receiver operating characteristic curve: 0.65 [95% confidence interval: 0.34-0.97], p = 0.40). These results show that eCO varies during EVLP. The interpretation of this variation and the role of eCO as a biomarker of ischemia reperfusion injuries during EVLP should be tested in further clinical studies.

Clinical Judgment Is Not Reliable for Reducing Whole-body Computed Tomography Scanning after Isolated High-energy Blunt Trauma.

BACKGROUND: The purpose of this study was to test the diagnostic performance of clinical judgment for the prediction of a significant injury with whole-body computed tomography scanning after high-energy trauma. METHODS: The authors conducted an observational prospective study in a single level-I trauma center. Adult patients were included if they had an isolated high-energy injury. Senior trauma leaders were asked to make a clinical judgment regarding the likelihood of a significant injury before performance of a whole-body computed tomography scan. Clinical judgments were recorded using a probability diagnosis scale. The primary endpoint was the diagnosis of a serious-to-critical lesion on the whole-body computed tomography scan. Diagnostic performance was assessed using receiver operating characteristic analysis. RESULTS: Of the 354 included patients, 127 patients (36%) had at least one injury classified as abbreviated injury score greater than or equal to 3. The area under the receiver operating characteristic curve of the clinical judgment to predict a serious-to-critical lesion was 0.70 (95% CI, 0.64 to 0.75%). The sensitivity of the clinical judgment was 82% (95% CI, 74 to 88%), and the specificity was 49% (95% CI, 42 to 55%). No patient with a strict negative clinical examination had a severe lesion (n = 19 patients). The sensitivity of the clinical examination was 100% (95% CI, 97 to 100%) and its specificity was 8% (95% CI, 5 to 13%). CONCLUSIONS: Clinical judgment alone is not sufficient to reduce whole-body computed tomography scan use. In patients with a strictly normal physical examination, whole-body computed tomography scanning might be avoided, but this result deserves additional study in larger and more diverse populations of trauma patients.