Comparison of Pressure Reactivity Index and Mean Velocity Index to Evaluate Cerebrovascular Reactivity During Induced Arterial Blood Pressure Variations in Severe Brain Injury.

OBJECTIVES: To compare the assessment of cerebral autoregulation by cerebrovascular reactivity indices based on intracranial pressure (Pressure Reactivity Index, PRx) and on transcranial Doppler (Mean Velocity Index, Mx) during controlled variations of arterial blood pressure in severe brain injury. Primary outcome was the agreement between both cerebrovascular reactivity indices measured by the Bland-and-Altman method. Secondary outcomes were the association of cerebrovascular reactivity indices with arterial blood pressure variation, and the comparison of optimal cerebral perfusion pressures determined by both indices. METHODS: All consecutive comatose (Glasgow Coma Scale < 8) patients from the surgical intensive care unit of Bicetre Hospital who had an acute brain injury on computerized tomography and needed vasopressor support were prospectively included. Step-by-step arterial pressure variations using vasopressors were performed to compare PRx and Mx and to calculate optimal cerebral perfusion pressure (CPPopt). MEASUREMENTS AND MAIN RESULTS: 15 patients were included. Mean difference between both indices measured by Bland-and-Altman plot was - 0.07 (IC 95% [- 1.02 to 0.87]). Mx was significantly associated with arterial pressure variation (one-way ANOVA test, p = 0.007), whereas PRx was not (p = 0.44). Optimal cerebral perfusion pressure calculated with PRx and Mx was respectively 11 and 15mmHg higher than the mean perfusion pressure prescribed. Optimal cerebral perfusion pressure calculation was possible in all cases. CONCLUSIONS: Cerebral vasoreactivity indices calculated with intracranial pressure or transcranial Doppler show only moderate agreement. Both indices nonetheless suggest substantially higher optimal cerebral perfusion pressure than those currently provided by international guidelines.

Early hyperoxemia is associated with lower adjusted mortality after severe trauma: results from a French registry.

BACKGROUND: Hyperoxemia has been associated with increased mortality in critically ill patients, but little is known about its effect in trauma patients. The objective of this study was to assess the association between early hyperoxemia and in-hospital mortality after severe trauma. We hypothesized that a PaO2 ≥ 150 mmHg on admission was associated with increased in-hospital mortality. METHODS: Using data issued from a multicenter prospective trauma registry in France, we included trauma patients managed by the emergency medical services between May 2016 and March 2019 and admitted to a level I trauma center. Early hyperoxemia was defined as an arterial oxygen tension (PaO2) above 150 mmHg measured on hospital admission. In-hospital mortality was compared between normoxemic (150 > PaO2 ≥ 60 mmHg) and hyperoxemic patients using a propensity-score model with predetermined variables (gender, age, prehospital heart rate and systolic blood pressure, temperature, hemoglobin and arterial lactate, use of mechanical ventilation, presence of traumatic brain injury (TBI), initial Glasgow Coma Scale score, Injury Severity Score (ISS), American Society of Anesthesiologists physical health class > I, and presence of hemorrhagic shock). RESULTS: A total of 5912 patients were analyzed. The median age was 39 [26-55] years and 78% were male. More than half (53%) of the patients had an ISS above 15, and 32% had traumatic brain injury. On univariate analysis, the in-hospital mortality was higher in hyperoxemic patients compared to normoxemic patients (12% versus 9%, p < 0.0001). However, after propensity score matching, we found a significantly lower in-hospital mortality in hyperoxemic patients compared to normoxemic patients (OR 0.59 [0.50-0.70], p < 0.0001). CONCLUSION: In this large observational study, early hyperoxemia in trauma patients was associated with reduced adjusted in-hospital mortality. This result contrasts the unadjusted in-hospital mortality as well as numerous other findings reported in acutely and critically ill patients. The study calls for a randomized clinical trial to further investigate this association.

Serratus Plane Block Is Effective for Pain Control in Patients With Blunt Chest Trauma: A Case Series.

BACKGROUND: Rib fractures occur frequently following blunt chest trauma and induce morbidity and mortality. Analgesia is a cornerstone for their management, and regional analgesia is one of the tools available to reach this objective. Epidural and paravertebral blocks are the classical techniques used, but the serratus plane block (SPB) has recently been described as an effective technique for thoracic analgesia. METHODS: This case series reported and analyzed 10 consecutive cases of SPB for blunt chest trauma analgesia in a level 1 trauma center from May to October 2018. SPB was performed with either a single shot of local anesthetic or a catheter infusion. RESULTS: Ten patients were treated with 3 single shots and 7 catheter infusions (median length 3 days [interquartile range (IQR) 2.5 to 3.5]). The Median Injury Severity Score was 16 (IQR 16 to 23), and the number of broken ribs ranged from 3 to 22. Daily equivalent oral morphine consumption was significantly decreased after SPB from 108 mg (IQR 67 to 120) to 19 mg (IQR 0 to 58) (P = 0.015). The Numeric Pain Rating Scale (NPRS) score during cough was significantly decreased from 7.3 (IQR 5.3 to 8.8) to 4 (IQR 3.6 to 4.6) (P = 0.03). The NPRS score at rest remained unchanged. One complication occurred, due to a catheter section. CONCLUSIONS: The SPB technique (with or without catheter insertion) in 10 patients who had blunt chest trauma with rib fractures is effective for cough pain control, with a significant decrease in morphine consumption.

A functional mini-GDE transgene corrects impairment in models of glycogen storage disease type III.

Glycogen storage disease type III (GSDIII) is a rare inborn error of metabolism affecting liver, skeletal muscle, and heart due to mutations of the AGL gene encoding for the glycogen debranching enzyme (GDE). No curative treatment exists for GSDIII. The 4.6 kb GDE cDNA represents the major technical challenge toward the development of a single recombinant adeno-associated virus-derived (rAAV-derived) vector gene therapy strategy. Using information on GDE structure and molecular modeling, we generated multiple truncated GDEs. Among them, an N-terminal-truncated mutant, ΔNter2-GDE, had a similar efficacy in vivo compared with the full-size enzyme. A rAAV vector expressing ΔNter2-GDE allowed significant glycogen reduction in heart and muscle of Agl-/- mice 3 months after i.v. injection, as well as normalization of histology features and restoration of muscle strength. Similarly, glycogen accumulation and histological features were corrected in a recently generated Agl-/- rat model. Finally, transduction with rAAV vectors encoding ΔNter2-GDE corrected glycogen accumulation in an in vitro human skeletal muscle cellular model of GSDIII. In conclusion, our results demonstrated the ability of a single rAAV vector expressing a functional mini-GDE transgene to correct the muscle and heart phenotype in multiple models of GSDIII, supporting its clinical translation to patients with GSDIII.

Gunshot and stab wounds in France: descriptive study from a national trauma registry.

PURPOSE: Severe trauma is a major problem worldwide. In France, blunt trauma (BT) is predominant and few studies are available on penetrating trauma (PT). The purpose of this study was to perform a descriptive analysis of severe gunshot (GSW) and stab wounds (SW) in patients who were treated in French trauma centers. METHODS: Retrospective study on prospectively collected data in a national trauma registry. All adult (> 15 years) trauma patients primarily admitted in 1 of the 17 trauma centers members of the Traumabase between January 2015 to December 2018 were included. Data from patients who had a PT were compared with those who had suffered a BT over the same period. Due to the known differences between GSW and SW, sub-group analyses on data from GSW, SW and BT were also performed. RESULTS: 8128 patients were included. Twelve percent of the study group had a PT. The main mechanism of PT was SW (68.1%). Five hundred and eighty patients with PT (59.4%) required surgery within the first 24 h. Severe hemorrhage was more frequent in penetrating traumas (11.2% vs. 7.8% p < 0.001). Hospital mortality following PT was 8.9% vs 11% for blunt trauma (p = 0.047). Among PT the mortality after GSW was ten times higher than after SW (23.8% vs 2%). CONCLUSION: This work is the largest study to date that has specifically focused on GSW and SW in France, and will help improving knowledge in managing such patients in our country.

Variations of Cutaneous Capnometry and Perfusion Index During a Heating Challenge is Early Impaired in Septic Shock and Related to Prognostic in Non-Septic Shock.

INTRODUCTION: In shock, the increase in cutaneous-to-arterial carbon dioxide partial pressure (Pc-aCO2) and the decrease in the perfusion index (PI) are related to macrovascular or microvascular alterations. We hypothesized that inducing cutaneous vasodilation and local perfusion with heat could provide a noninvasive tool to monitor microvascular reactivity. OBJECTIVES: This study aimed to develop a noninvasive approach, the heating challenge (HC), to monitor the microvascular reactivity of patients with shock and to evaluate the potential relationship with outcome. METHODS: After ethics committee agreement was obtained, 59 shock patients, including 37 septic shock, 22 non-septic shock (14 cardiogenic and eight hemorrhagic), 10 intensive care unit (ICU)-controls and 12 healthy volunteers, were included in this study. The HC consisted of heating the ear lobe PcCO2 sensor from 37° to 45° over 5 min and recording PcCO2 and PI variations (ΔPcCO2 and PImax/min). HC was performed on admission and during the first 48 h of hospitalization. RESULTS: Pc-aCO2 was significantly higher in shock patients than ICU-controls at baseline (P < 0.05). HC led to a decrease in PcCO2 and an increase in PI in the healthy volunteers (ΔPcCO2 = -9.0 ±â€Š4.6% and PImax/min = 5.5 ±â€Š1.9). On admission, non-septic shock patients (cardiogenic and hemorrhagic shocks) had an HC response profile identical to that of healthy volunteers and ICU-controls. In contrast, septic shock patients had a lower ΔPcCO 2 and PImax/min compared to healthy volunteers and all other groups (P < 0.05). After the first day, the combination of a Pc-aCO2 >17 mm Hg with a positive ΔPcCO2 could predict mortality with a specificity of 82% and a sensitivity of 93%. CONCLUSIONS: HC appears to be a dynamic test to classify vascular reactivity alterations in shock. At baseline, HC results were impaired in septic patients and conserved in non-septic patients. After the first day, the association between Pc-aCO2 and ΔPcCO2 was strongly related to prognosis in shock patients.

Opponency of astringent and fat sensations.

In most cultures, people ingest a variety of astringent foods and beverages during meals, but the reasons for this practice are unclear. Many popular beliefs and heuristics, such as high tannin wines should be balanced with fatty foods, for example 'red wine with red meat', suggest that astringents such as pickles, sorbets, wines, and teas 'cleanse' the palate while eating. Oral astringents elicit 'dry, rough' sensations [1], in part, by breaking down mucinous lubricating proteins in saliva [2,3]. The introduction of oral lubricants, including fats, partially diminishes strong astringent sensations [4,5]. Thus, it appears that astringency and fattiness can oppose each other perceptually on an oral rheological spectrum. Most teas, wines, and 'palate cleansers', however, are only mildly astringent and an explanation of how they could oppose the fattiness of meals is lacking. Here, we demonstrate that weakly astringent stimuli can elicit strong sensations after repeated sampling. Astringency builds with exposures [6] to an asymptotic level determined by the structure and concentration of the compound. We also establish that multiple sips of a mild astringent solution, similar to a wine or tea, decrease oral fat sensations elicited by fatty food consumption when astringent and fatty stimuli alternate, mimicking the patterning that occurs during a real meal. Consequently, we reveal a principle underlying the international practice of 'palate cleansing'. Repeatedly alternating samples of astringent beverages with fatty foods yielded ratings of fattiness and astringency that were lower than if rinsing with water or if presented alone without alternation.

Cutaneous ear lobe Pco2 at 37°C to evaluate microperfusion in patients with septic shock.

BACKGROUND: Tissue hypercarbia is related to hypoperfusion and microcirculatory disturbances in patients with septic shock. Transcutaneous Pco2 devices using a heated sensor to arterialize the tissue have been used as an alternative method for estimation of Paco2. This study investigates whether a cutaneous sensor attached to an ear lobe and regulated to 37°C could be used to measure cutaneous Pco2 (Pcco2) and evaluate microperfusion in patients with septic shock. METHODS: Fifteen stable patients in an ICU were studied as a control group. Forty-six patients with septic shock who were ventilated were enrolled as the study group. The difference of the gradients between Pcco2 and Paco2 (Pc-aco2) and between Pcco2 and end-tidal Pco2(Pc-etco2) were evaluated for 36 h. Variations of the Pc-aco2 and Pc-etco2 during fluid challenge were compared with microcirculatory skin blood flow (mBFskin) assessed by laser Doppler flowmetry. RESULTS: The baseline levels for Pc-aco2 and Pc-etco2 were significantly higher in the patients with septic shock than in the control group (14.8 [12.6] vs 6 [2.7] mm Hg and 25 [16.3] vs 9 [3.8] mm Hg, P < .0001, respectively). During the following 36 h, the Pc-aco2 and Pc-etco2 for the surviving patients with septic shock decreased significantly compared with the nonsurvivors (P < .01). The evolution of macrohemodynamic parameters showed no differences between survivors and nonsurvivors. At hour 24, a Pc-aco2 > 16 mm Hg and a Pc-etco2 > 26 mm Hg were related to poor outcome. Pc-aco2 and Pc-etco2 variations during fluid challenge were inversely correlated with changes in mBFskin (r² = 0.7). CONCLUSIONS: Ear lobe cutaneous Pco2 at 37°C represents a noninvasive technique to assess tissue Pco2 measurement. Pc-aco2 and Pc-etco2 were related to outcome and provide continuous information on microperfusion in patients with septic shock.