Protocolized reduction of non-resuscitation fluids versus usual care in septic shock patients (REDUSE): a randomized multicentre feasibility trial.

BACKGROUND/PURPOSE: Non-resuscitation fluids constitute the majority of fluid administered for septic shock patients in the intensive care unit (ICU). This multicentre, randomized, feasibility trial was conducted to test the hypothesis that a restrictive protocol targeting non-resuscitation fluids reduces the overall volume administered compared with usual care. METHODS: Adults with septic shock in six Swedish ICUs were randomized within 12 h of ICU admission to receive either protocolized reduction of non-resuscitation fluids or usual care. The primary outcome was the total volume of fluid administered within three days of inclusion. RESULTS: Median (IQR) total volume of fluid in the first three days, was 6008 ml (interquartile range [IQR] 3960-8123) in the restrictive fluid group (n = 44), and 9765 ml (IQR 6804-12,401) in the control group (n = 48); corresponding to a Hodges-Lehmann median difference of 3560 ml [95% confidence interval 1614-5302]; p < 0.001). Outcome data on all-cause mortality, days alive and free of mechanical ventilation and acute kidney injury or ischemic events in the ICU within 90 days of inclusion were recorded in 98/98 (100%), 95/98 (98%) and 95/98 (98%) of participants respectively. Cognition and health-related quality of life at six months were recorded in 39/52 (75%) and 41/52 (79%) of surviving participants, respectively. Ninety out of 134 patients (67%) of eligible patients were randomized, and 15/98 (15%) of the participants experienced at least one protocol violation. CONCLUSION: Protocolized reduction of non-resuscitation fluids in patients with septic shock resulted in a large decrease in fluid administration compared with usual care. A trial using this design to test if reducing non-resuscitation fluids improves outcomes is feasible. TRIAL REGISTRATION: Clinicaltrials.gov, NCT05249088, 18 February 2022. https://clinicaltrials.gov/ct2/show/NCT05249088.

Isocapnic hyperventilation provides early extubation after head and neck surgery: A prospective randomized trial.

BACKGROUND: Isocapnic hyperventilation (IHV) shortens recovery time after inhalation anaesthesia by increasing ventilation while maintaining a normal airway carbon dioxide (CO2 )-level. One way of performing IHV is to infuse CO2 to the inspiratory limb of a breathing circuit during mechanical hyperventilation (HV). In a prospective randomized study, we compared this IHV technique to a standard emergence procedure (control). METHODS: Thirty-one adult ASA I-III patients undergoing long-duration (>3 hours) sevoflurane anaesthesia for major head and neck surgery were included and randomized to IHV-treatment (n = 16) or control (n = 15). IHV was performed at minute ventilation 13.6 ± 4.3 L/min and CO2 delivery, dosed according to a nomogram tested in a pilot study. Time to extubation and eye-opening was recorded. Inspired (FICO2 ) and expired (FETCO2 ) CO2 and arterial CO2 levels (PaCO2 ) were monitored. Cognition was tested preoperatively and at 20, 40 and 60 minutes after surgery. RESULTS: Time from turning off the vapourizer to extubation was 13.7 ± 2.5 minutes in the IHV group and 27.4 ± 6.5 minutes in controls (P < .001). Two minutes after extubation, PaCO2 was 6.2 ± 0.5 and 6.2 ± 0.6 kPa in the IHV and control group respectively. In 69% (IHV) vs 53% (controls), post-operative cognition returned to pre-operative values within 40 minutes after surgery (NS). Incidences of pain and nausea/vomiting did not differ between groups. CONCLUSIONS: In this randomized trial comparing an IHV method with a standard weaning procedure, time to extubation was reduced with 50% in the IHV group. The described IHV method can be used to decrease emergence time from inhalation anaesthesia.

Renal tubular injury during cardiopulmonary bypass as assessed by urinary release of N-acetyl-ß-D-glucosaminidase.

BACKGROUND: Acute kidney injury (AKI) is a common complication with a major impact on morbidity and mortality after cardiac surgery with cardiopulmonary bypass (CPB). The aim of the present study was to perform a detailed analysis on the release of the tubular injury biomarker N-acetyl-b-D-glucosaminidase (NAG) during and early after CPB and to describe independent predictors of maximal tubular injury. We hypothesized that renal tubular injury occurs early after the onset of CPB. METHODS: In this prospective observational study, we included 61 patients undergoing open cardiac surgery with an expected CPB duration exceeding 60 min. The urinary NAG levels were measured at 30 min intervals during CPB, as well as early (30 min) after CPB and post-operatively. Independent predictors of tubular injury were identified using an Interquantile multivariate regression model. RESULTS: Already 30 min after the onset of CPB, NAG excretion was significantly increased (P < 0.001), followed by a sixfold peak increase after discontinuation of CPB (P < 0.001). In the multivariable regression model, CPB duration (P < 0.05) and the degree of rewarming during CPB (P < 0.05), were independent predictors of peak NAG excretion. CONCLUSION: In cardiac surgery, a renal tubular cell injury is seen early after onset of CPB with a peak biomarker increase early after end of CPB. The magnitude of this tubular injury is independently related to CPB duration and the degree of rewarming. Efforts made to decrease the CPB duration and to avoid hypothermia and the need for rewarming may decrease the risk for tubular injury.

Takotsubo syndrome in hemodynamically unstable patients admitted to the intensive care unit - a retrospective study.

INTRODUCTION: Takotsubo syndrome (TS) is an acute cardiac condition that is often triggered by critical illness but that has rarely been studied in the intensive care unit (ICU) setting. The aim of this study was to (i) estimate the incidence of TS in a hemodynamically unstable ICU-population; (ii) identify predictors of TS in this population; (iii) study the impact of TS on prognosis and course of hospitalization. METHODS: Medical records from all patients admitted to our general ICU from 2012 to 2015 were analyzed. TS was defined as having transient regional wall motion abnormalities (RWMA) with a typical pattern not attributable to a history of coronary artery disease or acute coronary syndromes. RESULTS: Out of 6470 patients admitted to the ICU, echocardiography due to hemodynamic instability was performed in 1051 patients; 467 had LV dysfunction and 59 fulfilled TS criteria. Patients with TS had higher SAPS 3 scores on admission than patients with normal LV function. Septic shock, cardiac arrest, cerebral mass lesion, female sex and low pH were independently associated with TS on admission. Patients with TS needed more ICU resources measured by higher NEMS scores and longer ICU-stay. Crude mortality was higher in TS patients (32%) vs the ICU-population (20%, P = 0.020), but there were no differences in a SAPS 3 adjusted analysis. CONCLUSION: TS was not an uncommon cause of LV dysfunction in hemodynamically unstable ICU-patients. Furthermore, TS was associated with a more complex disease. TS is a complication to take in consideration in the critically ill.

Perioperative COX-2 inhibitors may increase the risk of post-operative acute kidney injury.

BACKGROUND: In enhanced recovery protocols (ERP), a restrictive fluid regimen is proposed. Patients who undergo major surgery have an increased risk of post-operative acute kidney injury (AKI). This combination may pose difficulties when ERP is used for patients undergoing major surgery. The aim of this study was to evaluate whether patients undergoing pancreatic surgery and treated with a restrictive fluid regimen are at greater risk of post-operative AKI. Furthermore, if there was an increased risk of AKI, we aimed to identify its cause. METHODS: We reviewed the medical records of patients who underwent pancreatic surgery during 2014 (preERP, n = 58) and 2015 (ERP, n = 65). Fluid balance, the administration of cyclooxygenase-2 inhibitors, creatinine levels and mean arterial pressure were recorded. The Kidney Disease: Improving Global Outcomes criteria were used to define AKI. RESULTS: The incidence of AKI was higher in the ERP group than in the PreERP group (12.5% vs. 1.8%, respectively, P = 0.035). The increased incidence of AKI could not be explained by differences in comorbidities, age, pre-operative creatinine or perioperative hypotension. Administration of coxibs was higher in the ERP group and was associated with increased incidence of post-operative AKI (P = 0.018). The combination of coxibs and restrictive fluid regimen seems particularly harmful. CONCLUSION: Pancreatic surgery with a restrictive fluid regimen carries an increased risk of post-operative AKI if patients are also treated with cyclooxygenase-2 inhibitors. It is therefore suggested that in protocols including a restrictive fluid regimen for open pancreatic surgery, the use of cyclooxygenase-2 inhibitors should be avoided.

Post-operative pain relief using local infiltration analgesia during open abdominal hysterectomy: a randomized, double-blind study.

BACKGROUND: Post-operative pain is common and often severe after open abdominal hysterectomy, and analgesic consumption high. This study assessed the efficacy of local infiltration analgesia (LIA) injected systematically into different tissues during surgery compared with saline on post-operative pain and analgesia. METHODS: Fifty-nine patients were randomized to Group LIA (n = 29) consisting of 156 ml of a mixture of 0.2% ropivacaine + 30 mg ketorolac + 0.5 mg (5 ml) adrenaline, where the drugs were injected systematically in the operating site, around the proximal vagina, the ligaments, in the fascia and subcutaneously, or to saline and intravenous ketorolac, Group C (Control, n = 28), in a double-blind study. Post-operative pain, analgesic consumption, side-effects, and home discharge were analysed. RESULTS: Median dose of rescue morphine given 0-24 h after surgery was significantly lower in group LIA (18 mg, IQR 5-25 mg) compared with group C (27 mg, IQR 15-43 mg, P = 0.028). Median time to first analgesic injection was significantly longer in group LIA (40 min, IQR 20-60 min) compared with group C (20 min, IQR 12-30 min, P = 0.009). NRS score was lower in the group LIA compared with group C in the direct post-operative period (0-2 h). No differences were found in post-operative side-effects or home discharge between the groups. DISCUSSION: Systematically injected local infiltration analgesia for pain management was superior to saline in the primary endpoint, resulting in significantly lower rescue morphine requirements during 0-24 h, longer time to first analgesic request and lower early post-operative pain intensity.

Early treatment with isoflurane attenuates left ventricular dysfunction and improves survival in experimental Takotsubo.

BACKGROUND: Takotsubo syndrome (TS) is an acute cardiac condition, often triggered by critical illness, for which no specific treatment exists. Previously, we showed that isoflurane can prevent experimental TS. The aim of this study was to evaluate the potential treatment effects of isoflurane. Our primary hypothesis was that early treatment with isoflurane attenuates left ventricular akinesia in experimental TS. METHOD: In propofol-sedated animals, TS was induced by an intraperitoneal bolus of isoprenaline (50 mg/kg). Animals were randomized to one of six groups (n = 15 in each group), and 1% isoflurane was administered for 90 min in all groups. Isoflurane treatment was started at 0, 10, 30 (early treatment) or 120 (late treatment) minutes after isoprenaline injection. One additional late treatment group received isoflurane 0.5% for 180 min. A control group did not receive isoflurane. Left ventricular (LV) echocardiographic examination was performed at 90 min and 48 h after isoprenaline. Mortality was assessed at 48 h. RESULTS: Median degree of LV akinesia at 90 min was 24% in the control group and 0% in the early treatment groups (P < 0.001). Stroke volume, cardiac output and LV ejection fraction were higher in the early treatment groups vs. controls (P < 0.01). Mortality was lower in the early treatment groups (24%) vs. controls (86%) (P < 0.001). Mortality did not differ between the late treatment groups and controls. CONCLUSION: Early treatment with isoflurane attenuates the LV akinesia and improves survival in experimental TS. Isoflurane sedation in patients at risk of developing Takotsubo syndrome could be a subject for future studies.

Anaesthetic-induced cardioprotection in an experimental model of the Takotsubo syndrome - isoflurane vs. propofol.

BACKGROUND: Takotsubo syndrome (TS) is an acute cardiac condition with a substantial mortality for which no specific treatment is available. We have previously shown that isoflurane attenuates the development of left ventricular (LV) dysfunction in an experimental TS-model. We compared the effects of equi-anaesthetic doses of isoflurane, propofol and ketamine+midazolam on haemodynamics, global and regional LV systolic function and the activation of intracellular metabolic pathways in experimental TS. We hypothesized that cardioprotection in experimental TS is specific for isoflurane. METHODS: Forty-five rats were randomized to isoflurane (0.6 MAC, n = 15), propofol (bolus 200 mg/kg+360 mg/kg/h, n = 15) or ketamine (100 mg/kg)+midazolam (10 mg/kg, n = 15) anaesthesia. Arterial pressure, heart rate and body temperature were continuously measured and arterial blood gas analysis was performed intermittently. TS was induced by intraperitoneal injection of isoprenaline, 50 mg/kg. LV echocardiography was performed 90 min after isoprenaline injection. Apical cardiac tissue was analysed by global discovery proteomics and pathway analysis. RESULTS: Isoprenaline-induced changes in arterial blood pressure, heart rate or body temperature did not differ between groups. LV ejection fraction was higher and extent of LV akinesia was lower with isoflurane, when compared with the propofol and the ketamine+midazolam groups. In this TS-model, the proteomic analysis revealed an up-regulation of pathways involved in inflammation, coagulation, endocytosis and lipid metabolism. This up-regulation was clearly attenuated with isoflurane compared to propofol. CONCLUSION: In an experimental model of TS, isoflurane, but not propofol, exerts a cardioprotective effect. The proteomic analysis suggests that inflammation might be involved in pathogenesis of TS.

High-Sensitive Troponin T and N-Terminal Pro B-Type Natriuretic Peptide for Early Detection of Stress-Induced Cardiomyopathy in Patients with Subarachnoid Hemorrhage.

BACKGROUND: Patients developing stress-induced cardiomyopathy (SIC) after subarachnoid hemorrhage (SAH) have increased risk of vasospasm, delayed cerebral ischemia and death. We evaluated whether high-sensitive troponin T (hsTnT) and N-terminal pro B-type natriuretic peptide (NTproBNP) are useful biomarkers for early detection of SIC after SAH. METHODS: Medical records of all patients admitted to our NICU with suspected or verified SAH from January 2010 to August 2014 were reviewed. Patients in whom echocardiography was performed and blood samples for measurements of hsTnT and/or NTproBNP were obtained, within 72 and 48 h, respectively, after onset of symptoms, were included. SIC was defined as reversible left ventricular segmental hypokinesia diagnosed by echocardiography. RESULTS: A total of 502 SAH patients were admitted during the study period, 112 patients fulfilled inclusion criteria and 25 patients fulfilled SIC criteria. Peak levels of hsTnT and NTproBNP were higher in patients with SIC (p < 0.001). hsTnT had its peak on admission, while NTproBNP peaked at days 2-4 after onset of symptoms. A hsTnT > 89 ng/l or a NTproBNP > 2,615 ng/l obtained within 48 h after onset of symptoms had a sensitivity of 100% and a specificity of 79% in detecting SIC. CONCLUSIONS: The cardiac biomarkers, hsTnT and NTproBNP, are increased early after SAH and levels are considerably higher in patients with SIC. These biomarkers are useful for screening of SIC, which could make earlier diagnosis and treatment of SIC in SAH patients possible.