Norepinephrine Infusion Research Articles

Phenylephrine and norepinephrine increase blood pressure through opposing physiologic mechanisms in isoflurane-anesthetized dogs receiving acepromazine.

To elucidate the cardiovascular effects of escalating doses of phenylephrine and norepinephrine in dogs receiving acepromazine and isoflurane. 8 beagles aged 1 to 2 years (7.4 to 11.2 kg). All dogs received acepromazine 0.01 mg/kg, propofol 4 to 5 mg/kg, and isoflurane and were mechanically ventilated. Mean arterial pressure (MAP) from a femoral artery catheter and continuous electrocardiogram were recorded. Cardiac output (CO) was measured with transpulmonary thermodilution. Systemic vascular resistance (SVR), global end-diastolic volume (GEDV), and global ejection fraction (GEF) were subsequently calculated. Phenylephrine and norepinephrine were infused in random order at 0.07, 0.3, 0.7, and 1.0 μg/kg/min. All variables were measured after 15 minutes of each infusion rate. The effects of dose, agent, and their interaction on the change of each variable were evaluated with mixed-effect models. A P < .05 was used for significance. Atrial premature complexes occurred in 3 dogs during norepinephrine infusion at doses of 0.3, 0.7, and 1 μg/kg/min; no dysrhythmias were seen with phenylephrine administration. MAP increased during dose escalation (P < .0001) within each agent and did not differ between agents (P = .6). The decrease in HR was greater for phenylephrine (P < .0001). Phenylephrine decreased CO and GEF and increased GEDV and SVR (all P < .03). Norepinephrine decreased the SVR and increased CO, GEDV, and GEF (all P < .03). Our results confirm that phenylephrine increases arterial pressures mainly through vasoconstriction in acepromazine-premedicated dogs while norepinephrine, historically considered a vasopressor, does so primarily through an increase in inotropism.

Abstract P330: Two Rodent Models Of Augmented 24-hour Blood Pressure Variability Showing Similar Pathophysiological Features: Rats Infused With Norepinephrine Or Angiotensin II

Background: Augmented fluctuation of blood pressure (BP), so-called BP variability (BPV), was shown to be associated with cardiovascular diseases independently of BP levels. Recently we reported that 24-h BP variability is augmented in rats continuously infused with norepinephrine (NE) or angiotensin II (Ang II), assuming these animals as models of augmented BPV seen in ambulatory BP monitoring (ABPM) of humans. This study was aimed to clarify the underlying mechanisms for augmented BPV and the effects of azelnidipine, a calcium channel blocker, in rats infused with Ang II or NE. Methods and Materials: Nine-week-old male Wistar rats were continuously infused with subcutaneous 30 μg/h NE or 5.2 μg/h Ang II with or without oral administration with 30 mg/kg/day azelnidipine (Azl) for 14 days (n=8 to 9 per group). BPV was evaluated before and after 14 days of the infusions, using standard deviations (SDs) of systolic and diastolic BP (SBP and DBP) recorded every 15 min under an unrestrained condition by a radiotelemetry system. Baroreceptor reflex sensitivity (BRS) was quantified with a sequence analysis, while sections of the aortic arch, where baroreceptors are thought to be located, were microscopically evaluated by computerized measurement. Results: Both SBP and DBP rose following infusion of NE or Ang II, while these increases were attenuated by Azl (P&lt;0.01). SDs of SBP at the light (L) and dark (D) cycles were increased by NE (L, +94%; D, +117%, P&lt;0.01) and Ang II (L, +94%; D +95%, P&lt;0.01), with similar changes in SDs of DBP. These increases in SDs were attenuated following treatment with Azl almost to the control level (P&lt;0.01). Augmented BPVs in both the NE and Ang II groups were accompanied by reductions in BRS (P&lt;0.05) and by thickened medial area of the aortic arch (P&lt;.0.01), while Azl alleviated impairment of BRS and aortic medial thickening (P&lt;0.05). When analyzed for all groups by a simple regression, augmented BPV correlated with impairment of BRS (r=-0.54, P&lt;0.01), which was associated with aortic medial area (r=-0.56, P&lt;0.01). Conclusion: Rats infused chronically with NE or Ang II are models of increased 24-h BPV, both of which similarly showed impaired BRS and thickening medial layer of the aortic arch in association with augmented BPV.

Abstract P366: Natriuretic Peptides Potentiate Cardiac Hypertrophic Response To Norepinephrine In Rats

Background: The natriuretic peptide (NP) family consisting of ANP, BNP, and CNP is assumed to exert protective actions for the heart, alleviating hypertrophy and/or fibrosis of the myocardium. Excessive activation of the sympathetic nervous system is involved in cardiovascular damage including cardiac hypertrophy. In contrast to the previous notion, we show in the present study that both atrial and C-type natriuretic peptides (ANP and CNP) potentiate cardiac hypertrophic response to norepinephrine (NE) in rats. Methods and Materials: Nine-week-old male Wistar rats were continuously infused with subcutaneous 30 μg/h NE without or with persistent intravenous administration of either 1.0 μg/h ANP or CNP for 14 days. The NE plus ANP groups were treated orally without or with either 5 mg/day prazosin or 50 mg/day atenolol during this study period. Sample sizes are follows: control, NE, NE plus ANP, n=8 to 9; CNP, NE plus CNP, prazosin, atenolol, n=6 to 7. Blood pressure (BP) was recorded via a catheter placed in the abdominal aorta under an unrestrained condition by a radiotelemetry system. Cardiac hypertrophic response to NE was evaluated by heart weight to body weight (HW/BW) ratio. Left ventricular (LV) tissues were also examined microscopically to measure individual myocyte size and collagen deposition. Results: Mean BP levels at the light and dark cycles rose by 20 and 17 mmHg, respectively, following NE infusion for 14 days, with slight increases in HW/BW ratio (+7.6%) and ventricular myocyte size (+20%), compared to control (P&gt;0.05). Infusions of ANP and CNP had no significant effects on mean BP in NE-infused rats, while two natriuretic peptides potentiated cardiac hypertrophic response to NE at day 14 (HW/BW and myocyte size: NE plus ANP, +37% and +64%; NE plus CNP, +47% and +56%, respectively; P&lt;0.01 for all). No differences were noted in collagen volume fraction of LV among all study groups. Cardiac hypertrophy induced by co-administration of NE and ANP was attenuated by treatment with prazosin or atenolol. Conclusion: Both ANP and CNP potentiated α1- and β1-adrenergic receptor-mediated cardiac hypertrophic response to continuously infused NE in rats, suggesting a possible pro-hypertrophic action of NPs on the heart.

Comparison of crystalloid and colloid co-load combined with norepinephrine prophylaxis on post-spinal anesthesia hypotension during cesarean delivery: a randomized sequential allocation dose-finding study.

Fluid loading is an essential component of treatment for reducing the incidence of post-spinal anesthesia hypotension and is necessary to maintain intravascular volume, perfuse tissues, and control spinal anesthesia hypotension after sympathetic blockade. We performed a randomized sequential allocation dose-finding study to compare the effects of 10 mL/kg crystalloid and 6% hydroxyethyl starch (130/0.4) co-load on the ED90 of prophylactic norepinephrine infusion for preventing post-spinal anesthesia hypotension during cesarean delivery. Eighty patients were randomly allocated to receive either a 10 mL/kg crystalloid (Crystalloid Group, n = 40) or 6% hydroxyethyl starch (130/0.4) (Colloid Group, n = 40) co-load combined with prophylactic norepinephrine infusion during spinal anesthesia for cesarean delivery. The first patient received an initial prophylactic norepinephrine infusion rate of 0.025 μg/kg/min. Subsequent patients received a 0.005 μg/kg/min gradient dose of prophylactic norepinephrine. This dose was administered as a gradient based on its effectiveness for preventing post-spinal anesthesia hypotension (defined as SBP < 80% of baseline value) and determined by the up-and-down sequential allocation methodology. The primary study outcome was the ED90 of prophylactic norepinephrine infusion. Secondary outcomes included the incidence of post-spinal anesthesia hypotension, bradycardia, hypertension, Apgar scores, and umbilical artery blood gas values were also measured. The ED90 values of prophylactic norepinephrine infusion for preventing post-spinal anesthesia hypotension during cesarean delivery were 0.063 μg (95% CI: 0.050 to 0.064) and 0.062 μg (95% CI: 0.045 to 0.064) using isotonic regression analysis, and 0.068 μg (95% CI: 0.056 to 0.353) and 0.060 μg (95% CI: 0.050 to 3.590) using probit regression analysis in the Crystalloid Group and Colloid Group, respectively. The secondary outcomes were comparable between the two groups. The administration of a 10 mL/kg 6% hydroxyethyl starch (130/0.4) does not provide additional benefits compared to crystalloid co-load in reducing the ED90 of prophylactic norepinephrine infusion for preventing post-spinal anesthesia hypotension during cesarean delivery.

Norepinephrine corrected shock index as an innovative hemodynamic based prognosticator in critically ill patients

Background: Hemodynamic instability in critically ill patients can be assessed by various hemodynamic valid indicators. One of these approved hemodynamics’ prognosticator is the Shock Index (SI), which integrates both the heart rate and systolic blood pressure in one composite indicator. Arbitrarily, higher vasopressor rate indicates poorer prognostic. Whatever, Norepinephrine, the preferred vasopressor in most shock related scenarios, has a tendency to increase heart rate beside its vasoconstriction associated systolic blood pressure augmentation. Aim: In this study, we primarily aim to investigate the predictive power of a newer proposed composite hemodynamic prognosticator which integrates the average Norepinephrine infusion rates with the assessed patients’ Shock Indexes, and to explore its Sensitivity Indices regarding the critically ill patients’ major outcomes. Methods: This study trial was a non-funded, non-sponsored, observational study, which was conducted retrospectively on the Intensive Care Unit (ICU) at King Hussein Medical Center, Royal Medical Services, Amman, Jordan, over 60 months between Jan 2018 and Dec 2022. Exclusion criteria including but not excluded to, admission days less than 24 hours and missing data more than 80%. All eligible investigated critically ill patients were dichotomously divided into 2 comparative NE×SI products’ cohorts; lower product’s (NE×SI&lt;14.835 µg.bpm/min. mmHg) cohort (Cohort I) versus higher product’s (NE×SI≥14.835 µg.bpm/min. mmHg) cohort (Cohort II). A Chi Square test were conducted across these 2 dichotomized cohorts. The Binary Logistic Regression (BLgR) analysis was conducted for the tested patients’ prognosticator (NE×SI) against the probability of being allocated to the Non-Survivors State (The Positive State) rather than to the Survivors State (The Negative State). The Receiver Operating Characteristic (ROC) and Sensitivity Analysis were processed to explore the area under the ROC curves (AUROC±SEM), optimal cut-off points, and the other sensitivity indices. Results: Actually, 2528 and 3217 cases were processed as positive actual states (Positive OI, Non-Survivors) and as negative actual states (Negative OI, Survivors) respectively. The AUC±SEM for the NE×SI was significantly determined at 0.944±0.003 (95% CI; 0.938-0.949). The probability of the positive OI was 66.12% at the optimal operating cutoff point of 14.84 µg.bpm/min. mmHg. In this study, we constructed a BLgR model to prognosticate the admitted ICU patients’ mortality and was formulated as [e (-6.986+0.516× NE.SI) /1+ e (-6.986+0.516× NE.SI)]. Conclusion: Our results revealed that our proposed an innovative hemodynamic composited product had a reasonable constructed area under the curve with an interesting sensitivity index for prognosticating the admitted critically ill patients’ mortality rate.

Effect of norepinephrine on the vascular waterfall and tissue perfusion in vasoplegic hypotensive patients: a prospective, observational, applied physiology study in cardiac surgery

BackgroundNorepinephrine is a commonly used drug for treating vasoplegic acute circulatory failure in ICU. The prediction of norepinephrine macro- and micro-circulatory response is complicated by its uneven receptors’ distribution between the arterial and the venous structures, and by the presence of a physiological vascular waterfall (VW) that disconnects the arterial and the venous circulation in two pressure systems. The objectives of this study were to describe the VW in patients with arterial hypotension due to vasodilatory circulatory shock, and its behavior according to its response to norepinephrine infusion.MethodsA prospective, observational, bi-centric study has included adult patients, for whom the physician decided to initiate norepinephrine during the six first hours following admission to the ICU after cardiac surgery, and unresponsive to a fluid challenge. The mean systemic pressure (MSP) and the critical closing pressure (CCP) were measured at inclusion and after norepinephrine infusion.ResultsThirty patients were included. Norepinephrine increased arterial pressure and total peripheral resistances in all cohort. The cohort was dichotomized as VW responders (patients with a change of VW over the least significant change (≥ 93% increase in VW)), and as VW non-responders. In 19 (63%) of the 30 patients, VW increased from 3.47 [− 14.43;7.71] mmHg to 43.6 [25.8;48.1] mmHg, p < 0.001) with norepinephrine infusion, being classified as VW responders. The VW responders improved cardiac index (from 1.8 (0.6) L min−1 m−2 to 2.2 (0.5) L min−1 m−2, p = 0.002), capillary refill time (from to 4.2 (1.1) s to 3.1 (1) s, p = 0.006), and pCO2 gap (from 9 [7;10] mmHg to 6 [4;8] mmHg, p = 0.04). No baseline parameters were able to predict the VW response to norepinephrine. In comparison, VW non-responders did not significantly change the VW (from 5 [-5;16] mmHg to -2 [-12;15] mmHg, p = 0.17), cardiac index (from 1.6 (0.3) L min−1 m−2 to 1.8 (0.4) L min−1 m−2, p = 0.09) and capillary refill time (from 4.1 (1) s to 3.7 (1.4), p = 0.44).ConclusionsIn post-cardiac surgery patients with vasoplegic arterial hypotension, the vascular waterfall is low. Norepinephrine did not systematically restore the vascular waterfall. Increase of the vascular waterfall was associated with an improvement of laboratory and clinical parameters of tissue perfusion.

A Comparison of Dobutamine, Norepinephrine, Vasopressin, and Hetastarch for the Treatment of Isoflurane-Induced Hypotension in Healthy, Normovolemic Dogs.

Isoflurane is a commonly used inhalation anesthetic in species undergoing veterinary care that induces hypotension, impacting organ perfusion, making it imperative to minimize its occurrence or identify effective strategies for treating it. This study evaluated and compared the hemodynamic effects of DOB, NEP, VAS, and HES in twelve isoflurane-anesthetized Beagle dogs. The order of the first three treatments was randomized. HES was administered last. Data were collected before treatments (baseline) and after 10 min of a sustained MAP of <45 mmHg induced by a high end-tidal isoflurane concentration (T0). Once treatment was initiated and the target MAP was achieved (65 to 80 mmHg) or the maximum dose reached, data were collected after 15 min of stabilization (T1) and 15 min after (T2). A 15 min washout period with a MAP of ≥65 mmHg was allowed between treatments. The intravenous dosage regimens started and were increased by 50% every five minutes until the target MAP or maximum dose was reached. The dosages were as follows: DOB, 5-15 μg/kg/min; NEP, 0.1-2 μg/kg/min; VAS, 0.5-5 mU/kg/min; and HET, 6% 1-20 mL/kg/min. DOB improved CO, DO2, and VO2, but reduced SVR. VAS elevated SVR, but decreased CO, DO2, and VO2. HES minimally changed BP and mildly augmented CO, DO2, and VO2. These treatments failed to reach the target MAP. NEP increased the arterial BP, CO, MPAP, and PAWP, but reduced HR. Norepinephrine infusion at 0.44 ± 0.19 μg/kg/min was the most efficient therapy for correcting isoflurane-induced hypotension.

Cerebral autoregulation and cerebral blood flow response to mean arterial pressure challenge following induction of general anaesthesia for neuroradiology procedure

IntroductionIntraoperative hypotension is common following general anaesthesia induction with propofol, but its impact on cerebral autoregulation (CA) remains unclear. We investigate the incidence and risk factors of impaired CApost-propofol induction and its recovery after a mean arterial pressure (mAP) challenge.MethodsWe included 40 non-emergency neuroradiology surgery patients [58 (47, 58)years old., 57% women]. We recorded mAP, mean blood flow velocity in the mean cerebral artery (MCAvmean), and regional cerebral oxygen saturation (rSO2). We computed the mean flow index (Mxa) pre and post mAP challenge. Mxa &amp;gt; 0.3 defined poor CA.ResultsAfter anaesthesia induction, 21 (53%) had impaired CBF autoregulation (CA−, Mxa &amp;gt; 0.3). The average mAP was 66 ± 9 mmHg, average MCAv was 39 ± 12 cm.s−1, and rSO2 was 63 ± 7%. We found no significant difference in age, norepinephrine infusion rate, and cardiovascular risks factors were similar between CA− and CA+ (Mxa ≤ 0.3) patients. Among the 22 patients (CA−: n = 14; CA+: n = 8) undergoing mAP challenge, there was a significant Mxa improvement and MCAv increase among CA− patients, (CA−: 0.63 ± 0.18 vs. 0.28 ± 0.20, p &amp;lt; 0.001), and [absolute variation: 1 (0.7–1.5) vs. 7 (3–9) cm.sec−1], respectively.ConclusionAfter induction of general anaesthesia for neuroradiology procedure, 53% of the patients had an impaired CA, regardless of age or medical history. Importantly, a mAP challenge effectively restored CA and improved CBF.Clinical Trial Registrationidentifier, NCT04288869

Comparative study of norepinephrine and phenylephrine infusion for prophylaxis against post-spinal hypotension in patients undergoing elective cesarean section

Comparative study of norepinephrine and phenylephrine infusion for prophylaxis against post-spinal hypotension in patients undergoing elective cesarean section

Management of severe hypotension in a dog undergoing transvenous pacemaker implantation following acepromazine and subsequent terbutaline administration

AbstractThis case report describes events that occurred under general anaesthesia of a dog undergoing transvenous pacemaker implantation for third‐degree atrioventricular block. Following premedication with acepromazine and buprenorphine, general anaesthesia was induced with alfaxalone, and maintained with isoflurane in oxygen. The dog developed severe hypotension during the procedure with concurrent bradycardia before commencement of pacing. In order to increase the heart rate, terbutaline was administered intravenously. This was followed by a worsening of the hypotension, with only a small increase in heart rate. Blood pressure improved following noradrenaline infusion. The animal recovered uneventfully in intensive care, and was sedated due to its anxious temperament to avoid dislodgement of the pacemaker device in the postoperative period.

Endotoxic kidney injury in Beagle dogs assessed by serum creatinine and symmetric dimethylarginine, and urinary neutrophil gelatinase-associated lipocalin and clusterin

Sepsis of Gram negative bacterial origin results in lipopolysaccharide-induced endotoxemia. This often leads to acute kidney injury (AKI) and its recognition remains a challenge and delays treatment. As renal damage occurs before a rise in serum creatinine is detected, new early biomarkers of kidney injury need to be explored. The aim of this study was to determine changes in serum parameters of renal function and urine biomarkers of renal injury. This was a descriptive study. Endotoxemia was induced intravenously in six anaesthetized Beagles (T1). To achieve normotension, dogs received fluids (T2), followed by a continuous infusion of noradrenaline and dexmedetomidine or 0.9% NaCl (T3). Ten minutes later, the dogs received fluids (T4) and noradrenaline and dexmedetomidine or 0.9% NaCl in a crossover manner (T5). At each timepoint, blood and urine were collected for serum creatinine, urea, symmetric dimethylarginine, urine protein/creatinine (UPC) ratio, urine neutrophil-gelatinase-associated lipocalin (U-NGAL), U-NGAL/creatinine ratio, urine clusterin (U-clusterin) and U-clusterin/creatinine ratio. Data were analyzed using a mixed-effect model taking into account time and stage of veterinary AKI (VAKI). Three of six dogs had a VAKI stage ≥1; one with anuria and elevated creatinine. Serum creatinine (P < 0.001), U-NGAL/creatinine ratio (P = 0.01) and U-clusterin/creatinine ratio increased over time (P < 0.01). The UPC ratio (mean (range) 0.68 (0.35–2.3) versus 0.39 (0.15–0.71) P < 0.01) and U-NGAL (3164 pg/mL (100–147,555) versus 100 (100–14,524), P = 0.01) were higher in VAKI stage ≥1 versus stage 0, respectively. Endotoxemia induced VAKI stage ≥1 in half of the dogs. Repeated measurement of selected parameters could detect AKI early.

Time and Type of Administered Fluids during Cesarean Section Might Not Matter for Hemodynamic Outcomes, but There Are Significant Patient Safety Concerns Regarding Colloid Use in Parturients. Comment on Theodoraki et al. Colloid Preload versus Crystalloid Co-Load in the Setting of Norepinephrine Infusion during Cesarean Section: Time and Type of Administered Fluids Do Not Matter. J. Clin. Med. 2023, 12,

We read the article by Theodoraki K and colleagues entitled 'Colloid Preload versus Crystalloid Co-Load in the Setting of Norepinephrine Infusion during Cesarean Section: Time and Type of Administered Fluids Do Not Matter' with interest [...].

Reply to Akça, B.; Bilotta, F. Time and Type of Administered Fluids during Cesarean Section Might Not Matter for Hemodynamic Outcomes, but There Are Significant Patient Safety Concerns Regarding Colloid Use in Parturients. Comment on "Theodoraki et al. Colloid Preload versus Crystalloid Co-Load in the Setting of Norepinephrine Infusion during Cesarean Section: Time and Type of Administered Fluids Do Not

We would like to take this opportunity to thank Drs Akça and Bilotta for their interest and their insightful comments [...].

Comparing the hemodynamic effect of a large arteriovenous fistula during high and low cardiac output states.

Background: A large arteriovenous fistula (AVF) is a low-resistant circuit that affects organ perfusion and systemic hemodynamics even in standard conditions. The extent of its' effect in critical states has not been elucidated yet. We used norepinephrine to create systemic vasoconstriction, dobutamine to create high cardiac output, and rapid right ventricle pacing as a model of acute heart failure in a porcine model of high-flow AVF circulation. Methods: The protocol was performed on nine domestic female pigs under general anesthesia. AVF was created by connecting two high-diameter ECMO cannulas inserted in the femoral artery and vein. Continuous hemodynamic monitoring was performed throughout the protocol. Three interventions were performed-moderate dose of norepinephrine (0.25ug/kg/min), moderate dose of dobutamine (10ug/kg/min) and rapid right ventricle pacing to simulate low cardiac output state with mean arterial pressure under 60mmHg. Measurements were taken with opened and closed arteriovenous fistula. Results: Continuous infusion of norepinephrine with opened AVF significantly increased mean arterial pressure (+20%) and total cardiac output (CO) (+36%), but vascular resistance remained virtually unchanged. AVF flow (Qa) rise correlated with mean arterial pressure increase (+20%; R = 0.97, p = 0.0001). Effective cardiac output increased, leading to insignificant improvement in organ perfusion. Dobutamine substantially increased cardiac output with insignificant effect on AVF flow and mean arterial pressure. Carotid artery blood flow increased significantly after dobutamine infusion by approximately 30%, coronary flow velocity increased significantly only in closed AVF state. The effective cardiac output using the heart failure model leading to decrease of carotid artery flow and worsening of brain and peripheral tissue oximetry. AVF blood flow also dropped significantly and proportionally to pressure, but Qa/CO ratio did not change. Therefore, the effective cardiac output decreased. Conclusion: In abovementioned extreme hemodynamic conditions the AVF flow was always directly proportional to systemic perfusion pressure. The ratio of shunt flow to cardiac output depended on systemic vascular resistance. These experiments highlight the detrimental role of a large AVF in these critical conditions' models.

Prophylactic Fixed-Rate Phenylephrine Versus Norepinephrine Infusion in the Prevention of Post-spinal Anesthesia Hypotension During Cesarean Delivery.

Background Maternal hypotension following spinal anesthesia can be actively countered by the use of vasopressors. Prophylactic infusion of vasopressors with a rescue bolus dosing was observed to be more effective for hemodynamic stability when compared to administering a bolus dose alone. Although phenylephrine is the recommended drug to treat spinal hypotension, many recent studies have focussed on the role of norepinephrine infusions during cesarean section. In this study, we compared prophylactic fixed-rate intravenous infusions of phenylephrine and norepinephrine during cesarean delivery under spinal anesthesia and the requirement of intraoperative provider-administered rescue bolus of phenylephrine needed to overcome post-spinal anesthesia hypotension. Methodology A total of 208 patients undergoing elective cesarean section under spinal anesthesia were randomly assigned to two groups (group P and group N). Group N included 104 patients who received norepinephrine infusion at a rate of 2.5 μg/minute (0.04 μg/kg/minute), and group P included 104 patients who received phenylephrine infusion at a rate of 50 μg/minute (0.8 μg/kg/minute)to treat spinal hypotension. The primary outcome of our study was to compare the reduction in the number and total dose of intraoperative provider-administered rescue bolus of phenylephrine needed to maintain systolic blood pressure. The secondary outcome of our study was to compare the neonatal outcome using umbilical venous blood gas sampling and Apgar score at one and five minutes. Results The total number of phenylephrine rescue bolus required to treat hypotension was significantly lower in group N (p = 0.0005) compared to group P. The neonatal outcome was similar between the two groups. Conclusions Prophylactic norepinephrine infusion when compared to prophylactic phenylephrine infusion is associated with a lesser requirement of rescue phenylephrine boluses.

Effect of Peripherally Infused Norepinephrine on Reducing Central Venous Catheter Utilization.

The purpose of this retrospective study was to evaluate the impact of peripherally administered norepinephrine on avoiding central venous catheter insertion while maintaining safety of the infusion. An institutional guideline allows peripheral infusion of norepinephrine via dedicated, 16- to 20-gauge, mid-to-upper arm intravenous (IV) catheters for up to 24 hours. The primary outcome was the need for central venous access in patients initially started on peripherally infused norepinephrine. A total of 124 patients were evaluated (98 initially on peripherally infused norepinephrine vs 26 with central catheter only administration). Thirty-six (37%) of the 98 patients who were started on peripheral norepinephrine avoided the need for central catheter placement, which was associated with $8,900 in direct supply cost avoidance. Eighty (82%) of the 98 patients who started peripherally infused norepinephrine required the vasopressor for ≤12 hours. No extravasation or local complications were observed in any of the 124 patients, regardless of site of infusion. Administration of norepinephrine via a dedicated peripheral IV site appears safe and may lead to a reduction in the need for subsequent central venous access. To achieve timely resuscitation goals, as well as to minimize complications associated with central access, initial peripheral administration should be considered for all patients.

Norepinephrine infusion in brain dead organ donor: A retrospective study on its effects on graft function after renal transplant

Objective: To investigate the effect of vasoactive drugs use in brain-dead organ donors in renal recipient graft function. Material and Methods: Clinical data from 30 brain-dead organ donors, and 30 recipients in our center were analyzed retrospectively between July 2017 and November 2021. Results: Norepinephrine infusion was used in all 30 cadaveric donors, where 11 donors had inotropic combinations. Norepinephrine was infused at a median dose of 0.2mcg/kg/min. There was no relationship between duration and doses of norepinephrine in donors and graft rejection, graft loss, and dialysis requirement in renal recipients. Conclusion: Intravenous norepinephrine infusion below 0.2mcg/kg/min had no effect on graft function in the renal recipient, where fluid restitution was sufficient in the cadaveric donor. Keywords: brain dead, organ donors, vasoactive drugs, graft survival

Histological, Laboratorial, and Clinical Benefits of an Optimized Maintenance Strategy of a Potential Organ Donor-A Rabbit Experimental Model.

Most transplanted organs are obtained from brain-dead donors. Inflammation results in a higher rate of rejection. Objectives: The objective of this animal model of brain death (BD) was to evaluate the effect of the progressive institution of volume expansion, norepinephrine, and combined hormone therapy on clinical, laboratory, and histological aspects. Methods: Twenty rabbits were divided: A (control), B (induction of BD + infusion of crystalloid), C (BD + infusion of crystalloid and noradrenaline (NA)), and D (BD + infusion of crystalloid + vasopressin + levothyroxine + methylprednisolone + NA). The animals were monitored for four hours with consecutives analysis of vital signs and blood samples. The organs were evaluated by a pathologist. Results: In Group D, we observed fewer number and lesser volume of infusions (p = 0.032/0.014) when compared with groups B and C. Mean arterial pressure levels were higher in group D when compared with group B (p = 0.008). Group D had better glycemic control when compared with group C (p = 0.016). Sodium values were elevated in group B in relation to groups C and D (p = 0.021). In Group D, the organ perfusion was better. Conclusion: The optimized strategy of management of BD animals is associated with better hemodynamic, glycemic, and natremia control, besides reducing early signs of ischemia.

Vasoactive use in early goal-directed therapy in dogs with severe sepsis and septic shock

The goal of this study was to see how to evaluate the changes in macrovascularand microvascular parameters in survivors (Sv) and non-survivors (non-Sv) dogs with severe sepsis and septic shock (SEVS &amp;amp; SEPS) in response to goal-directed hemodynamic optimization at the intensive care unit (ICU), and to evaluate norepinephrine (NE) and dobutamine (DT) ICU applications, and their effectiveness for predicting death. Thirty-five dogs with SEVS &amp;amp; SEPS were used. NE was given to 10 hypotensive dogs, despite receiving a single bolus of fluid therapy, at a constant infusion rate of 1.5 µg/kg/min for 2 h. The rate of NE infusion was doubled (3.0 µg/kg/min) if the clinical response was insufficient after 2 hours. DT was administered to 5 dogs with left ventricular systolic dysfunction (LVSD) (LVS’&amp;lt;7.5 cm/s) at a constant infusion rate of 5 µg/kg/min for 2 h. The Sv and non-Sv groups had no major differences in macrovascular and microvascular characteristics, PW-TDI septal mitral annulus systolic (S') and early diastolic (E') velocities, or DT applications. The only difference was the use of NE applications. non-Sv received a greater amount of NE, while Sv received a smaller amount of NE. In contrast, more Sv received a greater amount of DT applications. Total mortality rate was 25.7%. In conclusion, the effects of DT and NE in dogs with SEVS &amp;amp; SEPS are limited. To provide evidence-based guidelines for dogs with SEVS &amp;amp; SEPS, more research is needed.

144-OR: Norepinephrine Mediates Severe Hypoglycemia–Induced Fatal Heart Block in Rats

Severe hypoglycemia can lead to fatal cardiac arrhythmias, specifically 3rd degree heart block. During hypoglycemia, the brain senses low glucose and activates the sympathetic nervous system leading to epinephrine and norepinephrine secretion. It is hypothesized that norepinephrine increases severe hypoglycemia induced fatal cardiac arrhythmias. To test this hypothesis, nondiabetic Sprague Dawley rats underwent hyperinsulinemic/severe hypoglycemic (10-15 mg/dl) clamps for 3 hours with continuous electrocardiogram recording. Rats were continuously infused with either 1) brain norepinephrine (ICV; n =15), 2) brain control (ICV aCSF; n = 11), 3) IV norepinephrine nerve terminal blocker (reserpine; n = 7), or 4) IV control (DMSO/saline; n = 6). Severe hypoglycemia induced mortality was increased to 40% with brain norepinephrine infusion compared to 27% in aCSF. Similarly, heart block was increased to 40% with brain norepinephrine infusion compared to 25% in aCSF (p &amp;lt; 0.05). Blockade of norepinephrine completely prevented mortality and heart block during severe hypoglycemia compared to 17% and 25% (p &amp;lt; 0.05), respectively, in controls. In summary, norepinephrine increases while blockade of norepinephrine prevents fatal heart block during severe hypoglycemia. Drugs that target norepinephrine action may have therapeutic potential in people with diabetes at risk for severe hypoglycemia. Disclosure E.H. Nuibe: None. M. Chambers: None. C.M. Reno-Bernstein: None. Funding National Institutes of Health (1R56HL160835-01); University of Utah