Canadian tertiary care pediatric massive hemorrhage protocols: a survey and comprehensive national review.

PURPOSE: Hemorrhage is the leading cause of pediatric death in trauma and cardiac arrest during surgery. Adult studies report improved patient outcomes using massive hemorrhage protocols (MHPs). Little is known about pediatric MHP adoption in Canada. METHODS: After waived research ethics approval, we conducted a survey of Canadian pediatric tertiary care hospitals to study MHP activations. Transfusion medicine directors provided hospital/patient demographic and MHP activation data. The authors extracted pediatric-specific MHP data from requested policy/procedure documents according to seven predefined MHP domains based on the literature. We also surveyed educational and audit tools. The analysis only included MHPs with pediatric-specific content. RESULTS: The survey included 18 sites (100% response rate). Only 13/18 hospitals had pediatric-specific MHP content: eight were dedicated pediatric hospitals, two were combined pediatric/obstetrical hospitals, and three were combined pediatric/adult hospitals. Trauma was the most common indication for MHP activation (54%), typically based on a specific blood volume anticipated/transfused over time (10/13 sites). Transport container content was variable. Plasma and platelets were usually not in the first container. There was little emphasis on balanced plasma/platelet to red-blood-cell ratios, and most sites (12/13) rapidly incorporated laboratory-guided goal-directed transfusion. Transfusion thresholds were consistent with recent guidelines. All protocols used tranexamic acid and eight sites used an audit tool. DISCUSSION/CONCLUSION: Pediatric MHP content was highly variable. Activation demographics suggest underuse in nontrauma settings. Our findings highlight the need for a consensus definition for pediatric massive hemorrhage, a validated pediatric MHP activation tool, and prospective assessment of blood component ratios. A national pediatric MHP activation repository would allow for quality improvement metrics.

RéSUMé: OBJECTIF: L'hémorragie est la principale cause de décès pédiatrique dans les cas de traumatismes et les arrêts cardiaques pendant la chirurgie. Les études menées chez l'adulte font état d'une amélioration des devenirs pour les patient·es lors de l'utilisation de protocoles d'hémorragie massive (PHM). On ne connait que peu de choses quant à l'adoption des PHM pédiatriques au Canada. MéTHODE: Après avoir été dispensés de l'approbation du comité d'éthique de la recherche, nous avons mené un sondage auprès des hôpitaux de soins tertiaires pédiatriques canadiens pour étudier les activations des PHM. Les directions responsables de la médecine transfusionnelle ont fourni des données démographiques sur les hôpitaux et la patientèle et sur l'activation des PHM. Nous avons extrait les données sur les PHM spécialement conçus pour les enfants à partir des documents de politiques et de procédures demandés selon sept domaines de PHM prédéfinis en nous fondant sur la littérature. Nous avons également examiné les outils éducatifs et de vérification. L'analyse n'a inclus que les PHM disposant d'un contenu spécifique à la pédiatrie. RéSULTATS: L'enquête comprenait 18 sites (taux de réponse de 100 %). Seuls 13/18 hôpitaux disposaient de contenu spécifique à la pédiatrie dans leurs PHM : huit étaient des hôpitaux pédiatriques dédiés, deux des hôpitaux pédiatriques/obstétricaux combinés, et trois des hôpitaux pédiatriques/adultes combinés. Le traumatisme était l'indication la plus fréquente d'activation d'un PHM (54 %), généralement fondé sur un volume sanguin spécifique anticipé/transfusé au fil du temps (10/13 sites). Le contenu du conteneur de transport était variable. Le plasma et les plaquettes n'étaient généralement inclus pas dans le premier récipient. Il n'y avait que peu d'emphase sur les ratios plasma/plaquettes et globules rouges équilibrés, et la plupart des sites (12/13) ont rapidement incorporé les protocoles de transfusion ciblée guidés par les tests sanguins de laboratoire. Les seuils de transfusion étaient conformes aux lignes directrices récentes. Tous les protocoles utilisaient de l'acide tranexamique et huit sites utilisaient un outil de vérification. DISCUSSION/CONCLUSION: Le contenu des PHM pédiatriques était très variable. Les données démographiques sur l'activation suggèrent une sous-utilisation dans les contextes non traumatiques. Nos résultats soulignent la nécessité d'une définition consensuelle de l'hémorragie massive pédiatrique, d'un outil d'activation pédiatrique validé du PHM et d'une évaluation prospective des ratios des composants sanguins. Un recueil national d'activation des PHM pédiatriques permettrait d'obtenir des mesures d'amélioration de la qualité.

Do nitric oxide synthase and cyclooxygenase contribute to the heat loss responses in older males exercising in the heat?

This study evaluated the separate and combined roles of nitric oxide synthase (NOS) and cyclooxygenase (COX) in forearm sweating and cutaneous vasodilatation in older adults during intermittent exercise in the heat. Twelve healthy older (62 ± 7 years) males performed two 30 min cycling bouts at a fixed rate of metabolic heat production (400 W) in the heat (35°C, 20% relative humidity). The exercise bouts were followed by 20 and 40 min of recovery, respectively. Forearm sweat rate (ventilated capsule) and cutaneous vascular conductance (CVC, laser Doppler perfusion units/mean arterial pressure) were evaluated at four skin sites that were continuously perfused via intradermal microdialysis with: (1) lactated Ringer solution (Control), (2) 10 mm ketorolac (non-selective COX inhibitor), (3) 10 mm N(G) -nitro-l-arginine methyl ester (l-NAME; non-selective NOS inhibitor) or (4) a combination of 10 mm ketorolac + 10 mm l-NAME. Sweating was not different between the four sites during either exercise bout (main effect P = 0.92) (average of last 5 min of second exercise, Control, 0.80 ± 0.06; ketorolac, 0.77 ± 0.09; l-NAME, 0.74 ± 0.07; ketorolac + l-NAME, 0.77 ± 0.09 mg min(-1) cm(-2) ). During both exercise bouts, relative to CVC evaluated at the Control site (average of last 5 min of second exercise, 69 ± 6%max), CVC was similar at the ketorolac site (P = 0.62; 66 ± 4%max) whereas it was attenuated to a similar extent at both the l-NAME (49 ± 8%max) and ketorolac + l-NAME (54 ± 8%max) sites (both P < 0.05). Thus, we demonstrate that NOS and COX are not functionally involved in forearm sweating whereas only NOS contributes to forearm cutaneous vasodilatation in older adults during intermittent exercise in the heat.

Greater energy demand of exercise during pregnancy does not impact mechanical efficiency.

Pregnant women are recommended to engage in 150 min of moderate-intensity physical activity per week to reduce pregnancy complications. Many women struggle to remain physically active throughout pregnancy, and there is no consensus about whether women adopt a less efficient movement pattern as they progress through pregnancy and experience gestational weight gain. This study assessed the change in energy expenditure and mechanical efficiency in pregnant women (PREG; n = 10) when performing a walking treadmill task in early, mid, and late pregnancy and also compared with an age- and body mass index-matched, nonpregnant (CON; n = 10) group. On average, the PREG group gained within the Institute of Medicine's gestational weight gain guidelines (11.6 ± 3.6 kg) and were all inactive (measured using accelerometry), except for 1 participant, by the third trimester, as per the 2019 Canadian physical activity guidelines for pregnant women. Energy expended to complete the walking task increased throughout pregnancy and was higher than the controls (111.5 ± 24.6 kcal) in mid and late pregnancy (139.0 ± 22.2 kcal, p = 0.02, and 147.3 ± 24.6 kcal, p = 0.005, respectively), but not early pregnancy (129.9 ± 18.9 kcal, p = 0.08). Walking mechanical efficiency was similar within pregnant women at each time point and compared to nonpregnant controls. Our findings add to the growing body of evidence demonstrating that pregnant women can safely perform physical activity by showing that walking mechanical efficiency is unchanged at low to moderate intensities. Novelty Energy demand during exercise increases proportionally to weight gain across pregnancy trimesters. However, mechanical efficiency remains unchanged during low- to moderate-intensity walking.

Effect of P2 receptor blockade on cutaneous vasodilation during rest and exercise in the heat in young men.

We assessed the role of purinergic P2 receptors in the regulation of cutaneous vasodilation in young adults at rest and during intermittent moderate-intensity exercise in the heat (35 °C). P2 receptor blockade augmented resting cutaneous vasodilation but had no influence during and following exercise. This increase was partly diminished by nitric oxide synthase inhibition. These results suggest a functional role of P2 receptors in the regulation of cutaneous vascular tone during ambient heat exposure at rest.

No effect of ascorbate on cutaneous vasodilation and sweating in older men and those with type 2 diabetes exercising in the heat.

Aging and chronic disease such as type 2 diabetes (T2D) are associated with impairments in the body's ability to dissipate heat. To reduce the risk of heat-related injuries in these heat vulnerable individuals, it is necessary to identify interventions that can attenuate this impairment. We evaluated the hypothesis that intradermal administration of ascorbate improves cutaneous vasodilation and sweating in older adults via nitric oxide synthase (NOS)-dependent mechanisms during exercise in the heat and whether these improvements, if any, are greater in individuals with T2D. Older males with (n = 12, 61 ± 9 years) and without (n = 12, 64 ± 7 years) T2D performed two 30-min bouts of cycling at a fixed rate of metabolic heat production of 500 W (~70% peak oxygen uptake) in the heat (35°C); each followed by a 20- and 40-min recovery, respectively. Cutaneous vascular conductance (CVC) and sweat rate were measured at four intradermal microdialysis sites treated with either (1) lactated Ringer (Control), (2) 10 mmol/L ascorbate (an antioxidant), (3) 10 mmol/L L-NAME (non-selective NOS inhibitor), or (4) a combination of ascorbate + L-NAME. In both groups, ascorbate did not modulate CVC or sweating during exercise relative to Control (all P > 0.05). In comparison to Control, L-NAME alone or combined with ascorbate attenuated CVC during exercise (all P ≤ 0.05) but had no influence on sweating (all P > 0.05). We show that in both healthy and T2D older adults, intradermal administration of ascorbate does not improve cutaneous vasodilation and sweating during exercise in the heat. However, NOS plays an important role in mediating cutaneous vasodilation.

iNOS-dependent sweating and eNOS-dependent cutaneous vasodilation are evident in younger adults, but are diminished in older adults exercising in the heat.

Nitric oxide synthase (NOS) contributes to sweating and cutaneous vasodilation during exercise in younger adults. We hypothesized that endothelial NOS (eNOS) and neuronal NOS (nNOS) mediate NOS-dependent sweating, whereas eNOS induces NOS-dependent cutaneous vasodilation in younger adults exercising in the heat. Further, aging may upregulate inducible NOS (iNOS), which may attenuate sweating and cutaneous vasodilator responses. We hypothesized that iNOS inhibition would augment sweating and cutaneous vasodilation in exercising older adults. Physically active younger (n = 12, 23 ± 4 yr) and older (n = 12, 60 ± 6 yr) adults performed two 30-min bouts of cycling at a fixed rate of metabolic heat production (400 W) in the heat (35°C). Sweat rate and cutaneous vascular conductance (CVC) were evaluated at four intradermal microdialysis sites with: 1) lactated Ringer (control), 2) nNOS inhibitor (nNOS-I, NPLA), 3) iNOS inhibitor (iNOS-I, 1400W), or 4) eNOS inhibitor (eNOS-I, LNAA). In younger adults during both exercise bouts, all inhibitors decreased sweating relative to control, albeit a lower sweat rate was observed at iNOS-I compared with eNOS-I and nNOS-I sites (all P < 0.05). CVC at the eNOS-I site was lower than control in younger adults throughout the intermittent exercise protocol (all P < 0.05). In older adults, there were no differences between control and iNOS-I sites for sweating and CVC during both exercise bouts (all P > 0.05). We show that iNOS and eNOS are the main contributors to NOS-dependent sweating and cutaneous vasodilation, respectively, in physically active younger adults exercising in the heat, and that iNOS inhibition does not alter sweating or cutaneous vasodilation in exercising physically active older adults.

Can intradermal administration of angiotensin II influence human heat loss responses during whole body heat stress?

It is unclear if angiotensin II, which can increase the production of reactive oxygen species (oxidative stress), modulates heat loss responses of cutaneous blood flow and sweating. We tested the hypothesis that angiotensin II-induced increases in oxidative stress impair cutaneous perfusion and sweating during rest and exercise in the heat. Eleven young (24 ± 4 yr) healthy adults performed two 30-min cycling bouts at a fixed rate of metabolic heat production (400 W) in the heat (35°C). The first and second exercises were followed by a 20- and 40-min recovery. Four microdialysis fibers were placed in the forearm skin for continuous administration of either: 1) lactated Ringer (control), 2) 10 µM angiotensin II, 3) 10 mM ascorbate (an antioxidant), or 4) a combination of 10 µM angiotensin II + 10 mM ascorbate. Cutaneous vascular conductance (CVC; laser-Doppler perfusion units/mean arterial pressure) and sweating (ventilated capsule) were evaluated at each skin site. Compared with control, angiotensin II reduced both CVC and sweating at baseline resting and during each recovery in the heat (all P < 0.05). However, during both exercise bouts, there were no differences in CVC or sweating between the treatment sites (all P > 0.05). When ascorbate was coinfused with angiotensin II, the effect of angiotensin II on sweating was abolished (all P > 0.05); however, its effect on CVC at baseline resting and during each recovery remained intact (all P < 0.05). We show angiotensin II impairs cutaneous perfusion independent of oxidative stress, while it impairs sweating through increasing oxidative stress during exposure to an ambient heat stress before and following exercise.