Continuous Administration Of Norepinephrine Research Articles

Mobilisation of critically ill patients receiving norepinephrine: a retrospective cohort study

BackgroundMobilisation and exercise intervention in general are safe and feasible in critically ill patients. For patients requiring catecholamines, however, doses of norepinephrine safe for mobilisation in the intensive care unit (ICU) are not defined. This study aimed to describe mobilisation practice in our hospital and identify doses of norepinephrine that allowed a safe mobilisation.MethodsWe conducted a retrospective single-centre cohort study of 16 ICUs at a university hospital in Germany with patients admitted between March 2018 and November 2021. Data were collected from our patient data management system. We analysed the effect of norepinephrine on level (ICU Mobility Scale) and frequency (units per day) of mobilisation, early mobilisation (within 72 h of ICU admission), mortality, and rate of adverse events. Data were extracted from free-text mobilisation entries using supervised machine learning (support vector machine). Statistical analyses were done using (generalised) linear (mixed-effect) models, as well as chi-square tests and ANOVAs.ResultsA total of 12,462 patients were analysed in this study. They received a total of 59,415 mobilisation units. Of these patients, 842 (6.8%) received mobilisation under continuous norepinephrine administration. Norepinephrine administration was negatively associated with the frequency of mobilisation (adjusted difference -0.07 mobilisations per day; 95% CI − 0.09, − 0.05; p ≤ 0.001) and early mobilisation (adjusted OR 0.83; 95% CI 0.76, 0.90; p ≤ 0.001), while a higher norepinephrine dose corresponded to a lower chance to be mobilised out-of-bed (adjusted OR 0.01; 95% CI 0.00, 0.04; p ≤ 0.001). Mobilisation with norepinephrine did not significantly affect mortality (p > 0.1). Higher compared to lower doses of norepinephrine did not lead to a significant increase in adverse events in our practice (p > 0.1). We identified that mobilisation was safe with up to 0.20 µg/kg/min norepinephrine for out-of-bed (IMS ≥ 2) and 0.33 µg/kg/min for in-bed (IMS 0–1) mobilisation.ConclusionsMobilisation with norepinephrine can be done safely when considering the status of the patient and safety guidelines. We demonstrated that safe mobilisation was possible with norepinephrine doses up to 0.20 µg/kg/min for out-of-bed (IMS ≥ 2) and 0.33 µg/kg/min for in-bed (IMS 0–1) mobilisation.

Association of Early Norepinephrine Administration With 24-Hour Mortality Among Patients With Blunt Trauma and Hemorrhagic Shock

Hemorrhagic shock is a common cause of preventable death after injury. Vasopressor administration for patients with blunt trauma and hemorrhagic shock is often discouraged. To evaluate the association of early norepinephrine administration with 24-hour mortality among patients with blunt trauma and hemorrhagic shock. This retrospective, multicenter, observational cohort study used data from 3 registries in the US and France on all consecutive patients with blunt trauma from January 1, 2013, to December 31, 2018. Patients were alive on admission with hemorrhagic shock, defined by prehospital or admission systolic blood pressure less than 100 mm Hg and evidence of hemorrhage (ie, prehospital or resuscitation room transfusion of packed red blood cells, receipt of emergency treatment for hemorrhage control, transfusion of >10 units of packed red blood cells in the first 24 hours, or death from hemorrhage). Blunt trauma was defined as any exposure to nonpenetrating kinetic energy, collision, or deceleration. Statistical analysis was performed from January 15, 2021, to February 22, 2022. Continuous administration of norepinephrine in the prehospital environment or resuscitation room prior to hemorrhage control, according to European guidelines. The primary outcome was 24-hour mortality, and the secondary outcome was in-hospital mortality. The average treatment effect (ATE) of early norepinephrine administration on 24-hour mortality was estimated according to the Rubin causal model. Inverse propensity score weighting and the doubly robust approach with 5 distinct analytical strategies were used to determine the ATE. A total of 52 568 patients were screened for inclusion, and 2164 patients (1508 men [70%]; mean [SD] age, 46 [19] years; median Injury Severity Score, 29 [IQR, 17-36]) presented with acute hemorrhage and were included. A total of 1497 patients (69.1%) required emergency hemorrhage control, 128 (5.9%) received a prehospital transfusion of packed red blood cells, and 543 (25.0%) received a massive transfusion. Norepinephrine was administered to 1498 patients (69.2%). The 24-hour mortality rate was 17.8% (385 of 2164), and the in-hospital mortality rate was 35.6% (770 of 2164). None of the 5 analytical strategies suggested any statistically significant association between norepinephrine administration and 24-hour mortality, with ATEs ranging from -4.6 (95% CI, -11.9 to 2.7) to 2.1 (95% CI, -2.1 to 6.3), or between norepinephrine administration and in-hospital mortality, with ATEs ranging from -1.3 (95% CI, -9.5 to 6.9) to 5.3 (95% CI, -2.1 to 12.8). The findings of this study suggest that early norepinephrine infusion was not associated with 24-hour or in-hospital mortality among patients with blunt trauma and hemorrhagic shock. Randomized clinical trials that study the effect of early norepinephrine administration among patients with trauma and hypotension are warranted to further assess whether norepinephrine is safe for patients with hemorrhagic shock.

Clinical case: congenital chylothorax and chyloperitoneum in a premature newborn

Congenital malformations of the heart and great vessels are found in 1% (1 in 100 newborns) among newborns. They are hold the second place after congenital malformations of the nervous system. One of these types of malformations are congenital malformations of the thoracic lymphatic duct. Unlike other anomalies of the great vessels, they are quite rare, and detected with a frequency of 1: 15000 newborns. A consequence of this prevalence of spontaneous chylothorax in newborns is a poorly understood problem in neonatology.Chylothorax is the most typical clinical manifestation of the thoracic lymphatic duct pathology, which is associated not only with congenital malformations. Nevertheless, the etiology and pathogenesis of spontaneous chylous effusion in newborns are unclear. Most often, chylothorax or chyloperitoneum occurs in premature infants.Today there are two ways of chylothrax treatment: conservative and surgical. In the past, for a long time, mortality from chylothorax has been 50-100%. Currently, with the introduction of modern methods of intensive care into practice, mortality from chylothorax in newborns, according to published data, has decreased to 30-50%, but remains quite high, which explains the significance of this pathology.The problem is also of clinical interest due to the small number of observations and the lack of a protocol for the management of chylothorax in newborns, especially in combination with chyloperitoneum and lymphedema.Nevertheless, this case report is interested due to achievement complete recovery of the patient, despite the pessimistic prognosis. The severity of the condition of the child required hospitalization in the neonatal intensive care unit and measures to support vital functions, drainage of the pleural cavity, octreotide infusion for 17 days, and chemical pleurodesis with 10% povidone-iodine solution.Analyzing this case, we noted the low efficiency of using only one particular method of therapy in the treatment of chylothorax and the rapid regression of symptoms after complex treatment, which was supplement with an invasive procedure - pleurodesis - in combination with the continuous administration of norepinephrine. Thus, due to this complex treatment this case distinguishes from standard recommendations.

Renal outcome after radical cystectomy and urinary diversion performed with restrictive hydration and vasopressor administration in the frame of an enhanced recovery program: A follow-up study of a randomized clinical trial

ObjectiveTo determine whether a restrictive perioperative fluid management in the context of an enhanced recovery after surgery program for radical cystectomy and urinary diversion affects renal function, as fluid restriction and the use of vasopressors have been linked to impaired tissue perfusion, potentially resulting in renal dysfunction. MethodsWe followed 166 patients initially included in a randomized clinical trial and equally allocated to receive a continuous norepinephrine administration combined with 1ml/kg/h initially, and after cystectomy 3ml/kg/h crystalloid infusion (intervention group, n = 83), or a standard crystalloid infusion of 6ml/kg/h throughout surgery (control group, n = 83). All patients followed our institutional enhanced recovery after surgery program. We prospectively assessed renal function (plasma creatinine values and estimated glomerular filtration rate Chronic Kidney Disease Epidemiology Collaboration equation) postoperatively. Decreased renal function was defined as a decrease in glomerular filtration rate is greater than 20% compared to preoperative values. ResultsThere was no significant difference in renal function between the groups postoperatively at any time point after discharge: diabetes mellitus (HR = 2.81 [95% CI: 1.48–5.36]; P = 0.002), preoperative estimated glomerular filtration rate (HR = 1.02 [95% CI: 1.00–1.03]; P = 0.007), and age (OR = 1.03 [95% CI: 11.00–1.06]; P = 0.038) were negative predictors for renal deterioration. ConclusionPostoperative renal function evolution was similar in patients receiving restrictive hydration with norepinephrine administration when compared to liberal hydration intraoperatively, suggesting that there is no influence of fluid management and administration of vasopressors on mid-term renal function.

The Effect of Norepinephrine Versus Epinephrine in Irrigation Fluid on the Incidence of Hypotensive/Bradycardic Events During Arthroscopic Rotator Cuff Repair With Interscalene Block in the Sitting Position

To compare the occurrence rate of hypotensive and bradycardic events (HBEs) during arthroscopic rotator cuff repair performed with interscalene brachial plexus block anesthesia in the sitting position in 2 groups of patients who underwent the procedure with norepinephrine or epinephrine added to the irrigation fluid. The secondary objective was to evaluate the efficacy of norepinephrine in comparison with epinephrine in controlling intraoperative bleeding and maintaining adequate visualization of the arthroscopic field of view during the procedure. We hypothesized that norepinephrine added to the irrigation fluid during shoulder arthroscopy in the sitting position would reduce the occurrence of HBEs, allowing optimal intraoperative bleeding control. One hundred twenty patients underwent an arthroscopic rotator cuff repair performed under peripheral anesthesia and in the beach-chair position. Patients were randomly divided into 2 groups of 60 cases each: Norepinephrine (0.66 mg/L) and epinephrine (0.33 mg/L) were added to irrigation bags in group N and group E, respectively. The primary outcome was the occurrence rate of HBEs during surgery. The secondary outcomes were timing of onset of HBEs, accompanying symptoms, and intraoperative bleeding that impaired arthroscopic visualization. The clarity of the visual field was rated postoperatively by the surgeon using a visual analog scale. Comparison between groups for all baseline variables and outcome measurements was performed with the χ(2) or Fisher exact test, as appropriate, for categorical variables and the Student t test or Mann-Whitney U test, as appropriate, for continuous variables. Significance was set at P < .05. One patient was excluded from group E because of block failure; therefore 119 patients were finally included in the study. Comparison between groups showed no significant differences in baseline characteristics. The occurrence rate of HBEs was significantly greater in group E (n= 15) than in group N (n= 5) (P= .02). No differences between groups were found in the average time of onset of HBEs, accompanying symptoms, and clarity of the visual field. Continuous administration of norepinephrine, 0.66 mg/L, diluted in irrigation fluid during arthroscopic rotator cuff repair with the patient in the beach-chair position reduces the incidence of HBEs and is as effective as epinephrine in controlling intraoperative bleeding and maintaining the visual clarity of the surgical field. Level I, randomized clinical study.

Superior Functional Outcome after Radical Cystectomy and Orthotopic Bladder Substitution with Restrictive Intraoperative Fluid Management: A Followup Study of a Randomized Clinical Trial

Continuous intraoperative norepinephrine infusion combined with restrictive deferred hydration improves surgical field visibility, and significantly decreases intraoperative blood loss and postoperative complications in patients undergoing radical cystectomy and urinary diversion. We determined whether the intraoperative fluid regimen would affect functional results (continence and erectile function) 1 year after orthotopic ileal bladder substitution. We analyzed a subgroup of 93 patients who received an ileal orthotopic bladder substitute. The subgroup was part of a randomized trial in 167 patients initially allocated to continuous norepinephrine administration starting with 2 μg/kg per hour combined with 1 ml/kg per hour initially and 3 ml/kg per hour crystalloid infusion after cystectomy (norepinephrine/low volume group of 51) or a standard crystalloid infusion of 6 ml/kg per hour throughout surgery (42 controls). We prospectively assessed daytime and nighttime continence, and erectile function 1 year postoperatively in the 93-patient subgroup. Daytime continence was reported by 44 of 51 patients (86%) in the norepinephrine/low volume group and by 27 of 42 controls (64%) (p = 0.016), and nighttime continence was reported by 38 (75%) and 25 (60%), respectively (p = 0.077). Erectile function recovery was reported by 26 of 33 preoperatively potent patients (79%) in the norepinephrine/low volume group and by 11 of 29 controls (38%) (p = 0.002). Patients who undergo radical cystectomy and orthotopic bladder substitution with continuous norepinephrine infusion and restrictive hydration during surgery have significantly better daytime continence and erectile function 1 year postoperatively.

Intraoperative Continuous Norepinephrine Infusion Combined with Restrictive Deferred Hydration Significantly Reduces the Need for Blood Transfusion in Patients Undergoing Open Radical Cystectomy: Results of a Prospective Randomised Trial

BackgroundOpen radical cystectomy (ORC) is associated with substantial blood loss and a high incidence of perioperative blood transfusions. Strategies to reduce blood loss and blood transfusion are warranted. ObjectiveTo determine whether continuous norepinephrine administration combined with intraoperative restrictive hydration with Ringer's maleate solution can reduce blood loss and the need for blood transfusion. Design, setting, and participantsThis was a double-blind, randomised, parallel-group, single-centre trial including 166 consecutive patients undergoing ORC with urinary diversion (UD). Exclusion criteria were severe hepatic or renal dysfunction, congestive heart failure, and contraindications to epidural analgesia. InterventionPatients were randomly allocated to continuous norepinephrine administration starting with 2μg/kg per hour combined with 1ml/kg per hour until the bladder was removed, then to 3ml/kg per hour of Ringer's maleate solution (norepinephrine/low-volume group) or 6ml/kg per hour of Ringer's maleate solution throughout surgery (control group). Outcome measurements and statistical analysisIntraoperative blood loss and the percentage of patients requiring blood transfusions perioperatively were assessed. Data were analysed using nonparametric statistical models. Results and limitationsTotal median blood loss was 800ml (range: 300–1700) in the norepinephrine/low-volume group versus 1200ml (range: 400–2800) in the control group (p<0.0001). In the norepinephrine/low-volume group, 27 of 83 patients (33%) required an average of 1.8 U (±0.8) of packed red blood cells (PRBCs). In the control group, 50 of 83 patients (60%) required an average of 2.9 U (±2.1) of PRBCs during hospitalisation (relative risk: 0.54; 95% confidence interval [CI], 0.38–0.77; p=0.0006). The absolute reduction in transfusion rate throughout hospitalisation was 28% (95% CI, 12–45). In this study, surgery was performed by three high-volume surgeons using a standardised technique, so whether these significant results are reproducible in other centres needs to be shown. ConclusionsContinuous norepinephrine administration combined with restrictive hydration significantly reduces intraoperative blood loss, the rate of blood transfusions, and the number of PRBC units required per patient undergoing ORC with UD.

Changes in Serum S100A12 and sRAGE Associated with Improvement of the PaO2/FiO2 Ratio following PMX-DHP Therapy for Postoperative Septic Shock

Background: Endotoxin (Et) adsorption therapy with a column of polymyxin B-immobilized fibers (PMX) is effective in improving the partial pressure of arterial oxygen/fraction of inspired oxygen ratio (PaO₂/FiO₂ ratio) and increasing mean arterial blood pressure (MAP) in sepsis. S100A12 and soluble receptor for advanced glycation end product (sRAGE) are useful as early markers of acute lung injury. Purpose: To investigate the effect of improving the PaO₂/FiO₂ ratio by PMX-direct hemoperfusion (PMX-DHP) on production of S100A12 and sRAGE. Subjects and Methods: Sepsis patients after surgery for perforation of the lower gastrointestinal tract were adopted as the subjects. We retrospectively reviewed the cases of 20 patients on mechanical ventilation and continuous administration of norepinephrine. We recorded PaO₂/FiO₂ ratio, MAP, and norepinephrine doses. S100A12, sRAGE, and Et levels were measured before and after PMX-DHP. Results: The PaO₂/FiO₂ ratio and MAP improved significantly after PMX-DHP (p < 0.05). S100A12 and Et decreased significantly after PMX-DHP (p < 0.05). No differences were observed in sRAGE. Conclusion: S100A12 is useful as a marker that reflected improvement in the PaO₂/FiO₂ ratio after PMX-DHP. We consider PMX-DHP to be useful as adjunctive therapy for sepsis that reduces the Et and corrects the pathology in the early stage.

Effects of alterations in arterial CO2 tension on cerebral blood flow during acute intracranial hypertension in rats.

Cerebrovascular reactivity to CO2 in clinical and experimental studies has been found to be impaired during increased intracranial pressure (ICP). However, from previous study results it has not been possible to estimate whether the impairment was caused by elevated ICP, or caused by decreased cerebral perfusion pressure (CPP). The current study was carried out in a group of unmanipulated control rats and in six investigation groups of six rats each: two groups with elevated ICP (30 and 50 mm Hg) and spontaneous arterial blood pressure (MABP), two groups with spontaneous ICP and arterial hypotension (77 and 64 mm Hg), and two groups with elevated ICP (30 and 50 mm Hg) and arterial hypertension (124 mm Hg). Intracranial hypertension was induced by continuous infusion of lactated Ringer's solution into the cisterna magna, arterial hypotension by controlled bleeding, and arterial hypertension by continuous administration of norepinephrine intravenously. Cerebral blood flow (CBF) was measured repetitively by the intraarterial 133Xe method at different levels of arterial PCO2. In each individual animal, CO2 reactivity was calculated from an exponential regression line obtained from the corresponding CBF/PaCO2 values. By plotting each individual value of CO2 reactivity against the corresponding CPP value from the seven investigation groups, CPP was significantly and directly related to CO2 reactivity of CBF (P < .001). No correlation was found by plotting CO2 reactivity values against the corresponding MABP values or the corresponding ICP values. Thus, the results show that CO2 reactivity is at least partially determined by CPP and that the impaired CO2 reactivity observed at intracranial hypertension and arterial hypotension may be caused by reduced CPP.

Biogenic Amines Regulate Avian Immunity

Alzet mini-osmotic pumps were implanted subcutaneously to administer norepinephrine (NE) and epinephrine (E) to 6-wk-old line UNH 105 chickens. Dose-time studies showed the most effective NE and E dose and exposure time on two chicken cellular immune responses: the phytohemagglutinin (PHA) wattle response and leukocyte migration. Administration of 1 μg/h NE for 72 h suppressed significantly the wattle stimulation index [2.48 ± .3 (SE)] compared to that of saline controls (4.1 ± .3) but enhanced mean leukocyte migration (7.7 ± .3 versus 4.9 ± .3). Epinephrine at 1 μg/h for 72 h significantly suppressed the wattle index (1.8±.2) compared to that of controls (2.8±.3) but E at 1 μg/h for 48 h enhanced leukocyte migration (9.5 ± .2 versus 6.4 ± .2). Continuous administration of NE and E at physiological levels alters cell-mediated immunity and appears to have an immune regulatory role in the chicken.

Sex ratio of offsprings of rats bred at 5 degrees C.

The sex ratio at birth was examined in offsprings of rats reared in 5°C for successive generations. The sex ratio of their offsprings significantly skewed toward females and the litter size markedly reduced, as compared with those of controls reared in 22°C. Continuous administration of norepinephrine for 12 weeks which purports to simulate a cold stress resulted in a reduction of litter size with a tendency of skewness in sex ratio toward females.

Effects of continuous administration of angiotensin II on ventricular performance

The effects of angiotensin II on circulatory dynamics and coronary blood flow were studied in the cat. With equal single doses of angiotensin II and norepinephrine a greater blood pressure response occurred with angiotensin. With continuous administration of angiotensin II a large initial blood pressure response occurred, but rapidly returned to an intermediate value. During this time the animal was refractory to further single doses. A sustained large increase of ventricular contractility was readily demonstrated with the continuous administration of norepinephrine, but could not be demonstrated with equal amounts of angiotensin II. Acute transient changes of ventricular contractility were observed. Frequently an acute increase of both stroke work at a given filling pressure, and mean rate of ejection occurred. Occasionally, however, marked acute myocardial depression, which rapidly returned to control values, was observed. In about one-third of the preparations prolonged myocardial depression was observed following a period of continuous angiotensin II infusion. This was in sharp contrast to continuous norepinephrine infusion following which myocardial depression was never observed. Measurements of coronary blood flow indicated that when ventricular work was maintained constant, continuous angiotensin II infusion was frequently associated with a transient reduction of coronary flow. This was usually small, but occasionally marked. During this phase concomitant myocardial depression was evident. Continuous norepinephrine infusion produced only an increase of coronary blood flow with an associated increase of myocardial contractility.