Perioperative Supplemental Oxygen and Plasma Catecholamine Concentrations After Major Abdominal Surgery – a Substudy of a Randomized Clinical Trial

BackgroundIncreased sympathetic nerve activity due to perioperative stress is associated with higher plasma catecholamine concentrations that lead to an increase in heart rate and blood pressure. This fact plays a pivotal role in the development of perioperative myocardial ischemia. A previous study in healthy volunteers has shown that the administration of supplemental oxygen attenuated sympathetic nerve activity, which was associated with lower plasma catecholamine concentrations. However, in patients undergoing surgery evidence is still lacking. We therefore tested the hypothesis that perioperative supplemental oxygen attenuates sympathetic nerve activity estimated by plasma catecholamines in patients at risk for cardiovascular complications undergoing major abdominal surgery.MethodsWe randomly assigned 81 patients to receive either 80% versus 30% inspired oxygen concentration throughout surgery and for the first two postoperative hours. We assessed noradrenaline, adrenaline and dopamine plasma concentrations as surrogate parameters for sympathetic nerve activity before induction of anesthesia, two hours after surgery and on the third postoperative day.Results41 patients received 80% oxygen and 40 patients received 30% oxygen. There was no significant difference in postoperative noradrenaline (effect estimated:-41.5 ng.L-1, 95%CI -134.3, 51.2; p=0.38), adrenaline (effect estimated:11.2 ng.L-1, 95%CI -7.6, 30.1; p=0.24) and dopamine (effect estimated:-1.61 ng.L-1, 95%CI -7.2, 3.9; p=0.57) concentrations between both groups. ConclusionsWe found no significant difference in postoperative plasma catecholamine concentration between the 80% and 30% oxygen group in patients at risk for cardiovascular complications undergoing major abdominal surgery. Based on our results, it seems likely that supplemental oxygen did not influence sympathetic nerve activity in the perioperative setting.Trial RegistrationClinicalTrials.gov (NCT 03366857)European Clinical Trial Database (EudraCT 2017-003714-68)

Prophylactic use of intravenous tramadol vs intravenous nalbuphine for control of postspinal shivering after knee arthroscopy: a randomized double-blind placebo controlled trial

Background Post-anesthetic shivering refers to spontaneous, involuntary, rhythmic, oscillating and tremor-like muscle hyperactivity that increases metabolic heat production up to 600% after general or regional anesthesia. Shivering is not only subjectively unpleasant but is physiologically stressful because it elevates blood pressure, heart rate, oxygen consumption, and plasma catecholamine concentrations. Moreover, shivering may aggravate pain and hinder wound closure by simply stretching surgical incisions. Objective The aim of this work is to compare the efficacy of intravenous tramadol VS nalbuphine for prevention of post spinal shivering during knee arthroscopy. Methods This prospective randomized double blinded study was carried in Ain Shams University hospitals on 90 patients scheduled for knee arthroscopy. Patients were randomized into three groups 30 patients each: Group C: patients received normal saline 0.9%) intravenously. Group T: Patients received Tramadol 0.5 mg/kg intravenously. Group N: Patients received nalbuphine 0.1mg/kg intravenously. All drugs were given immediately after intra thecal injection of the anaesthetic drugs and returning to the supine position. Results The study revealed that the incidence of shivering was less in the tramadol (23.3%) and nalbuphine (26.7%) groups compared to the saline group (56.7%) (P < 0.05) with no significant difference between Nalbuphine and Tramadol groups (p > 0.05). The mean grade of shivering was comparable between the three groups (P > 0.05). Shivering onset was significantly earlier in the saline group (24.1±2.9 min) compared to Nalbuphine (32.3±4.9min) and Tramadol (36.4±4.3min) groups (P < 0.05) with no significant difference between Nalbuphine and Tramadol groups (p > 0.05). There were no significant differences among the three groups as regards hemodynamics (Heart rate and mean blood pressure), respiratory rate, oxygen saturations, body temperature, the incidence of nausea or vomiting (P > 0.05). While sedation grade was significantly highest in Nalbuphine group followed by Tramadol group and least in Saline group (P < 0.001). Conclusion The current study revealed that both tramadol 0.5mg/kg and balbuphine 0.1mg/kg was effective in prevention of post spinal shivering in patients undergoing knee arthroscopy.

A prospective randomized controlled trial comparing the effects of dexmedetomidine and fentanyl on attenuation of pressor response during laryngoscopy and intubation in neurosurgical patients

Background: Laryngoscopy is associated with a sympathetic response that results in a rapid increase in blood pressure and heart rate in these patients. The mechanisms underlying these hemodynamic changes are incompletely understood. They may be caused by a reflex sympathetic discharge due to stimulation of the upper respiratory tract. It has been observed that hemodynamic responses to tracheal intubation are associated with an increase in plasma catecholamine concentrations and are attenuated by β-adrenergic blockade. These hemodynamic changes may be undesirable particularly in neurosurgical patients. Aim of the study is the present study was prospective, randomized, double-blind conducted to evaluate the efficacy of dexmdetomidine and fentanyl in attenuation of pressor responses to laryngoscopy and intubation in neurosurgical patients undergoing lumbar spine surgeries.Methods: A total of 60 patients of 18–65 years, American Society of Anaesthesiologists Class I/II of undergoing elective neurosurgical procedures were included in the study. The patients were divided into two groups of 30 patients each. Group D received dexmedetomidine and Group F received Fentanyl. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MAP) were recorded preoperatively (baseline), at 5 and 8 minutes after infusion of study drug, before induction, 1 minute after induction, 2 minute after intubation, 5 minute after intubation, 10 minute after intubation and 15 minute after intubation.Results: There was a better control of Heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure in Group D when compared to Group F during laryngoscopy and after intubation.Conclusions: The present study shows that dexmedetomidine suppresses hemodynamic responses effectively than fentanyl.

Fuel selection during short-term submaximal treadmill exercise in the cold is not affected by pre-exercise low-intensity shivering

Exercise and shivering rely on different metabolic pathways and consequently, fuel selection. The present study examined the effects of a pre-exercise low-intensity shivering protocol on fuel selection during submaximal exercise in a cold environment. Nine male subjects exercised 4 times for 60 min at 50% (LOW) or 70% (MOD) of their peak oxygen consumption on a motorized treadmill in a climatic chamber set at 0 °C with (SHIV) and without (CON) a pre-exercise cooling protocol, inducing low-intensity shivering. Thermal, cardiorespiratory and metabolic responses were measured every 15 min whereas blood samples were collected every 30 min to assess serum nonesterified fatty acids (NEFA), glycerol, glucose, β-hydroxybutyrate (BHB) and plasma catecholamine concentrations. Rectal and skin temperatures were lower in the SHIV condition, within LOW and MOD conditions, during the first 45 min of exercise. Norepinephrine (NE) concentration was greater in SHIV vs. CON within LOW (1.39 ± 0.17 vs. 0.98 ± 0.17 ng·mL−1) and MOD (1.50 ± 0.20 vs. 1.01 ± 0.09 ng·mL−1), whereas NEFA, glycerol and BHB were greater in SHIV vs. CON (1060 ± 49 vs. 898 ± 78 μmol·L−1; 0.27 ± 0.02 vs. 0.22 ± 0.03 mmol·L−1; 0.39 ± 0.06 vs. 0.27 ± 0.04 mmol·L−1, respectively) within MOD only. No changes were observed in fat or carbohydrate oxidation between SHIV and CON during exercise. Despite increases in NE, NEFA, glycerol and BHB from pre-exercise low-intensity shivering, fuel selection during short-term submaximal exercise in the cold was unaltered.

Adrenergic Response to Maximum Exercise of Trained Road Cyclists

The aim of this study was to evaluate adrenergic responses in the peripheral blood of trained road cyclists at rest, at maximal intensity of incremental bicycle exercise test, and during 15 minutes of recovery, as well as the relationship between them. Competitive male road cyclists, in the pre-competitive phase of a season, mean age 21.7 ± 6.4 years, and BMI 20.7 ± 0.8 kg·m-2, performed an incremental test on a bicycle ergometer with unloaded cycling for 5 min, then increased the load to 40 W every 3 min, up to maximal exercise intensity. The plasma catecholamine concentrations (epinephrine, norepinephrine) and oxygen uptake were estimated. The expression of 132 genes related to the adrenergic system in leukocytes was measured. A statistically significant increase in plasma epinephrine concentration (p < 0.01) was observed in response to exercise. The mean of maximal oxygen uptake was 65.7 ± 5.5 ml·kg-1·min-1. The RGS2 gene expression was highest regardless of the test phase for all athletes. The effort had a statistically significant influence on ADRB2 and RAB2A expression. In addition, the RAB2A, ADM and HSPB1 expression level increased during recovery. We can conclude that plasma epinephrine concentration and genes related to the adrenergic system such as ADM, ADRB2, CCL3, GPRASP1, HSPB1, RAB2A, RGS2 and ROCK1 seem to have an influence on the response to high-intensity exercise in trained cyclists.

Abstract 57: Therapeutic Effects of Small Molecule Gβγ Inhibition in Pressure Overload Heart Failure

Heart failure (HF) is a progressive disease with rapidly increasing rates of morbidity and mortality; it is the leading cause of death worldwide. Elevated sympathetic nervous system activity, a salient feature of HF progression, leads to pathologic attenuation and desensitization of β-adrenergic receptors (β-ARs) due in part to Gβγ-mediated signaling. We recently reported that novel small molecule Gβγ inhibitors selectively block specific Gβγ signals and halt HF progression in pharmacologic and transgenic mouse models of HF. We assessed the hypothesis that the Gβγ inhibitor Gallein could be salutary in treating pre-existing HF in a clinically relevant model. We utilized the pressure-overload HF model of mouse transverse aortic constriction (TAC). Four weeks post-TAC, mice received daily IP injections of vehicle (PBS; group V) or Gallein (10mg/Kg/day; group G) for eight weeks. Gallein treatment improved survival (7 of 9 mice survived vs. 5 of 9 mice in group V) and cardiac function (%EF 75.2 ± 7.5 vs 35.6 ± 17.2 in group V, +dP/dt (mmHg/sec) 7022 ± 485.3 vs. 3584 ± 598.6 in group V), -dP/dt (mmHg/sec) -5826 ± 910.7 vs. -3260 ± 62.3 in group V, LVEDP (mmHg) 11.5 ± 3.7 vs. 29.45 ± 3.6 in group V). In addition, gallein reduced cardiac hypertrophy (HW/BW (mg/g) 5.8 ± 0.3 vs. 8.8 ± 1.1 in group V) and plasma catecholamine concentrations (adrenaline (ng/ml) 1.3 ± 0.3 vs. 6.6 ± 2.8 in group V, noradrenaline (ng/ml) 3.6 ± 0.6 vs. 15.1 ± 3.6 in group V). Reduction of interstitial fibrosis as well as mRNA levels of α-SMA, TNF-α, and IL-6 was observed in the hearts of Gallein treated animals (59.7 ± 14.1%, 43.8 ± 9.3% and 28.5 ± 3.5% relative to group V, respectively). On the molecular level, Gallein treated mice showed less GRK2 and PI3Kγ membrane recruitment, and less Akt activation (42.9 ± 7.1%, 66.7 ± 13.3% and 46.2 ± 7.7% relative to group V, respectively) in myocardial lysates. In conclusion , these data suggest a possible therapeutic role for small molecule Gβγ inhibition in halting the progression of HF, potentially via inhibition of the Gβγ-GRK2-PI3Kγ-Akt pathway. The combined effect of halting HF progression and reducing plasma catecholamines suggests a possible systemic role for small molecule Gβγ inhibition in both the heart and the adrenal gland.

Influence de la phase du cycle menstruel sur les réponses en catécholamines à l’exercice de sprint chez la femme

The aim of the present study was to verify the menstrual cycle phase influence on catecholamine concentrations (adrenaline (A) and noradrenaline (NA)), peak power (Ppic), and peak lactatemia (Lapic) in response to a 6 s sprint exercise on a cycle ergometer in eight untrained women (19.1 ± 0.9 years, 167.7 ± 5.4 cm, 59.5 ± 4.7 kg). All women realize the 6 s sprint test in the morning, within the same menstrual cycle, in the follicular (PF) and the luteal phase (PL). Plasma catecholamine concentrations were determined at rest (A0 and NA0), immediately at the end of the sprint exercise (AEX and NAEX), and after 5 min of recovery (A5 and NA5). Ppic and Lapic were not significantly affected by the menstrual cycle phase. Catecholamine concentrations measured at rest, in response to the 6 s sprint test and after 5 min of recovery were not significantly different in PF and PL. Significant relationships were observed between AEX and Lapic (r = 0.53, p < 0.01) and between AEX and Ppic (r = 0.70, p < 0.01). In conclusion, this study demonstrated that the menstrual cycle phase did not alter performance, lactatemia, and sympatho-adrenergic responses to a short sprint exercise in untrained women.