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1.
Blood Purif ; : 1-10, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34515056

RESUMO

AIM: The aim of this study was to investigate the association of hyperoncotic (20%) human albumin solution (HAS) with outcomes among critically ill patients receiving continuous renal replacement therapy (RRT). METHODS: Analysis of the Randomized Evaluation of Normal versus Augmented Level (RENAL) RRT trial data. RESULTS: Of 1,508 patients, 771 (51%) received albumin. Of these, 345 (45%) received 4% HAS only, 155 (20%) received 20% HAS only, and 271 (35%) received both. Patients who received combined 4% and 20% HAS were more severely ill, received more days of RENAL trial therapy and required mechanical ventilation for longer. Mean daily fluid balance was -288 mL (-904 to 261) with 20% HAS only versus 245 mL (-248 to 1,050) with 4% HAS only (p < 0.001). On Cox proportional hazards regression, 20% HAS exposure was not associated with greater 90-day mortality (odds ratio 1.12, 95% confidence interval [CI]: 0.77-1.62; p = 0.55) or longer recovery to RRT independence (sub-hazard ratio 1.04, 95% CI: 0.84-1.30; p = 0.70) compared to those who received 4% HAS only. CONCLUSIONS: RENAL trial patients commonly received albumin in varying concentrations. The administration of 20% HAS was associated with a more negative fluid balance but was not independently associated with increased mortality or RRT dependence when compared to 4% HAS only.

2.
Anesth Analg ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34543256

RESUMO

BACKGROUND: Acute kidney injury requiring renal replacement therapy (AKI-RRT) is strongly associated with mortality after cardiac surgery; however, options for early identification of patients at high risk for AKI-RRT are extremely limited. Early after cardiac surgery, the predictive ability for AKI-RRT even of one of the most extensively evaluated novel urinary biomarkers, neutrophil gelatinase-associated lipocalin (NGAL), appears to be only moderate. We aimed to determine whether the NGAL/hepcidin-25 ratio (urinary concentrations of NGAL divided by that of hepcidin-25) early after surgery may compare favorably to NGAL for identification of high-risk patients after cardiac surgery. METHODS: This is a prospective substudy of the BICARBONATE trial, a multicenter parallel-randomized controlled trial comparing perioperative bicarbonate infusion for AKI prevention to usual patient care. At a tertiary referral center, 198 patients at increased kidney risk undergoing cardiac surgery with cardiopulmonary bypass were included into the present study. The primary outcome measure was defined as AKI-RRT. Secondary outcomes were in-hospital mortality and long-term mortality. We compared area under the curve of the receiver operating characteristic (AUC-ROC) of urinary NGAL with that of the urinary NGAL/hepcidin-25 ratio within 60 minutes after end of surgery. We compared adjusted AUC and performed cross-validated reclassification statistics of the (logarithmic) urinary NGAL/hepcidin-25 ratio adjusted to Cleveland risk score/EuroScore, cross-clamp time, age, volume of packed red blood cells, and (logarithmic) urinary NGAL concentration. The association of the NGAL/hepcidin-25 ratio with long-term patient survival was assessed using Cox proportional hazard regression analysis adjusting for EuroScore, aortic cross-clamp time, packed red blood cells and urinary NGAL. RESULTS: Patients with AKI-RRT (n = 13) had 13.7-times higher NGAL and 3.3-times lower hepcidin-25 concentrations resulting in 46.9-times higher NGAL/hepcidin-25 ratio early after surgery compared to patients without AKI-RRT. The NGAL/hepcidin-25 ratio had higher AUC-ROC compared with NGAL for risk of AKI-RRT and in-hospital mortality (unadjusted AUC-ROC difference 0.087, 95% confidence interval [CI], 0.036-0.138, P < .001; 0.082, 95% CI, 0.018-0.146, P = .012). For AKI-RRT, the NGAL/hepcidin-25 ratio increased adjusted category-free net reclassification improvement (cfNRI; 0.952, 95% CI, 0.437-1.468; P < .001) and integrated discrimination improvement (IDI; 0.040, 95% CI, 0.008-0.073; P = .016) but not AUC difference. For in-hospital mortality, the ratio improved AUC of the reference model (AUC difference 0.056, 95% CI, 0.003-0.108; P = .037) and cfNRI but not IDI. The urinary NGAL/hepcidin-25 ratio remained significantly associated with long-term mortality after adjusting for the model covariates. CONCLUSIONS: The urinary NGAL/hepcidin-25 ratio appears to early identify high-risk patients and outperform NGAL after cardiac surgery. Confirmation of our findings in other cardiac surgery centers is now needed.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34543581

RESUMO

RATIONALE: The continuous infusion of fentanyl or morphine is often prescribed to assist with analgesia and sedation (analgosedation) during mechanical ventilation. OBJECTIVES: To compare the effect of fentanyl vs. morphine on patient-centered outcomes in ventilated patients. METHODS: We conducted a cluster-randomized, cluster-crossover trial between July 2019 and August 2020 in two adult Intensive Care Units. We compared two continuous infusion regimens (fentanyl vs. morphine). One Intensive Care Unit was randomized to the fentanyl-morphine sequence and the other to the morphine-fentanyl sequence. The primary outcome was the number of ventilator free days at day 28. Secondary outcomes included, among others, duration of mechanical ventilation in survivors and Intensive Care Unit free days at day 28. MEASUREMENTS AND MAIN RESULTS: Via cluster allocation, we randomized 737 patients. Of these, 56 were excluded due to the opt-out consent process, leaving 681 (344 to fentanyl and 337 to morphine) for primary analysis (median [IQR] age, 59 [44-69] years). Median ventilator free days at day 28 were 26.1 (20.7-27.3) in the fentanyl vs 25.3 (19.1-27.2) in the morphine group (median difference, 0.79 [95% CI, 0.31 to 1.28], p=0.001). Intensive Care Unit-free days were greater (P<0.001) and Intensive Care Unit length of stay in survivors shorter (P<0.001) in the fentanyl group. All other secondary outcomes were not statistically different by treatment group. CONCLUSIONS: Among adult patients requiring mechanical ventilation, compared with morphine, fentanyl infusion significantly increased the median number of ventilator free days at day 28. The choice of opioid infusion agent may affect clinical outcomes and requires further investigation. Clinical trial registration available at https://www.anzctr.org.au/, ID: ACTRN12619000939190.

5.
Blood Purif ; : 1-8, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521084

RESUMO

BACKGROUND: Continuous renal replacement therapy (CRRT) is a form of dialysis used in critically ill patients, and has recently been associated with renal nonrecovery. Decreases in platelets following CRRT initiation are common and are associated with mortality, but associations with renal recovery are unclear. Our objective was to determine if platelet nadir or the degree of platelet decrease following CRRT initiation was associated with renal nonrecovery. METHODS: This is a secondary analysis of the Randomized Evaluation of Normal versus Augmented Level (RENAL) trial. Primary predictors were platelet nadir discretized by median value and percent platelet decrease following CRRT initiation, with cut points evaluated by decile from 30 to 60%. The 2 primary outcomes were time to RRT-independence and RRT-free days. Secondary outcomes were 28-day mortality, 90-day mortality, intensive care unit (ICU)-free, and hospital-free days. RESULTS: Time to RRT independence censored for death was achieved less frequently in patients with low platelet nadir (hazard ratio [HR] 0.77, confidence interval [CI] 0.66-0.91) and in those with >50% platelet decrease (HR 0.84, CI 0.72-0.97). RRT-free days were lower in both low platelet nadir (odds ratio [OR] 0.94, CI 0.90-0.97) and >50% platelet decrease (OR 0.91, CI 0.88-0.95). These groups also had higher rates of 28- and 90-day mortality and fewer ICU-free and hospital-free days. Thrombocytopenia at CRRT initiation was also associated with renal nonrecovery, although the clinical effect was small. CONCLUSIONS: Platelet nadir <100 × 103/µL and platelet decrease by >50% following CRRT initiation were both associated with lower rates of renal recovery. Further research is needed to evaluate mechanisms-linking platelet changes and renal nonrecovery in CRRT.

6.
Ann Am Thorac Soc ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380007

RESUMO

RATIONALE: Hypercapnia may affect the outcome of sepsis. Very few clinical studies conducted in non-critically ill patients, have investigated the effects of hypercapnia and hypercapnic acidemia in the context of sepsis. The effect of hypercapnia in critically ill patients with sepsis remains inadequately studied. OBJECTIVE: To investigate the association of hypercapnia with hospital mortality in septic critically ill patients. METHODS: This is a retrospective study conducted in three tertiary public hospitals. Septic critically ill patients from three intensive care units between January 2011 and May 2019 were included. Five cohorts (exposure of at least 24, 48, 72, 120 and 168 hours) were created to account for immortal time bias and informative censoring. The association between hypercapnia exposure and hospital mortality was assessed with multivariable models. Subgroup analyses compared ventilated vs. non-ventilated and pulmonary vs. non-pulmonary sepsis patients. RESULTS: We analyzed 84,819 PaCO2 measurements in 3,153 patients (57.6% male; median age was 62.5 years). After adjustment for key confounders, both in mechanically ventilated and non-ventilated patients and in patients with pulmonary sepsis, there was no independent association of hypercapnia with hospital mortality. In contrast, in ventilated patients, the presence of prolonged exposure to both hypercapnia and acidemia was associated with increased mortality (highest Odds Ratio of 16.5 for at least 120 hours of potential exposure; P = 0.007). CONCLUSION: After adjustment, isolated hypercapnia was not associated with increased mortality in septic patients. These hypothesis-generating observations suggest that as hypercapnia is not an independent risk factor for mortality, trials of permissive hypercapnia in sepsis may be safe.

7.
Acta Physiol (Oxf) ; 231(4): e13596, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-34347356

RESUMO

AIM: Renal tissue hypoxia during cardiopulmonary bypass could contribute to the pathophysiology of acute kidney injury. We tested whether renal tissue hypoxia can be alleviated during cardiopulmonary bypass by the combined increase in target pump flow and mean arterial pressure. METHODS: Cardiopulmonary bypass was established in eight instrumented sheep under isoflurane anaesthesia, at a target continuous pump flow of 80 mL·kg-1 min-1 and mean arterial pressure of 65 mmHg. We then tested the effects of simultaneously increasing target pump flow to 104 mL·kg-1 min-1 and mean arterial pressure to 80 mmHg with metaraminol (total dose 0.25-3.75 mg). We also tested the effects of transitioning from continuous flow to partially pulsatile flow (pulse pressure ~15 mmHg). RESULTS: Compared with conscious sheep, at the lower target pump flow and mean arterial pressure, cardiopulmonary bypass was accompanied by reduced renal blood flow (6.8 ± 1.2 to 1.95 ± 0.76 mL·min-1 kg-1) and renal oxygen delivery (0.91 ± 0.18 to 0.24 ± 0.11 mL·O2 min-1 kg-1). There were profound reductions in cortical oxygen tension (PO2) (33 ± 13 to 6 ± 6 mmHg) and medullary PO2 (31 ± 12 to 8 ± 8 mmHg). Increasing target pump flow and mean arterial pressure increased renal blood flow (to 2.6 ± 1.0 mL·min-1 kg-1) and renal oxygen delivery (to 0.32 ± 0.13 mL·O2 min-1kg-1) and returned cortical PO2 to 58 ± 60 mmHg and medullary PO2 to 28 ± 16 mmHg; levels similar to those of conscious sheep. Partially pulsatile pump flow had no significant effects on renal perfusion or oxygenation. CONCLUSIONS: Renal hypoxia during experimental CPB can be corrected by increasing target pump flow and mean arterial pressure within a clinically feasible range.


Assuntos
Pressão Arterial , Ponte Cardiopulmonar , Animais , Hipóxia , Oxigênio , Circulação Renal , Ovinos
8.
Clin Nutr ; 40(8): 5047-5052, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34388414

RESUMO

BACKGROUND: Hypophosphatemia may be a useful biomarker to identify thiamine deficiency in critically ill enterally-fed patients. The objective was to determine whether intravenous thiamine affects blood lactate, biochemical and clinical outcomes in this group. METHOD: This randomized clinical trial was conducted across 5 Intensive Care Units. Ninety critically ill adult patients with a serum phosphate ≤0.65 mmol/L within 72 h of commencing enteral nutrition were randomized to intravenous thiamine (200 mg every 12 h for up to 14 doses) or usual care (control). The primary outcome was blood lactate over time and data are median [IQR] unless specified. RESULTS: Baseline variables were well balanced (thiamine: lactate 1.2 [1.0, 1.6] mmol/L, phosphate 0.56 [0.44, 0.64] mmol/L vs. control: lactate 1.0 [0.8, 1.3], phosphate 0.54 [0.44, 0.61]). Patients randomized to the intervention received a median of 11 [7.5, 13.5] doses for a total of 2200 [1500, 2700] mg of thiamine. Blood lactate over the entire 7 days of treatment was similar between groups (mean difference = -0.1 (95 % CI -0.2 to 0.1) mmol/L; P = 0.55). The percentage change from lactate pre-randomization to T = 24 h was not statistically different (thiamine: -32 (-39, -26) vs. control: -24 (-31, -16) percent, P = 0.09). Clinical outcomes were not statistically different (days of vasopressor administration: thiamine 2 [1, 4] vs. control 2 [0, 5.5] days; P = 0.37, and deaths 9 (21 %) vs. 5 (11 %); P = 0.25). CONCLUSIONS: In critically ill enterally-fed patients who developed hypophosphatemia, intravenous thiamine did not cause measurable differences in blood lactate or clinical outcomes. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12619000121167).

9.
Perfusion ; : 2676591211037025, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34405746

RESUMO

INTRODUCTION: Postoperative atrial fibrillation (POAF) is common after cardiac surgery and associated with increased hospital length of stay, patient morbidity and mortality. We aimed to identify factors associated with POAF and evaluate the accuracy of available POAF prediction models. METHODS: We screened articles from Ovid MEDLINE® and PubMed Central® (PMC) and included studies that evaluated risk factors associated with POAF or studies that designed or validated POAF prediction models. We only included studies in cardiac surgical patients with sample size n ⩾ 50 and a POAF outcome group ⩾20. We summarised factors that were associated with POAF and assessed prediction model performance by reviewing reported calibration and discriminative ability. RESULTS: We reviewed 232 studies. Of these, 142 fulfilled the inclusion criteria. Age was frequently found to be associated with POAF, while most other variables showed contradictory findings, or were assessed in few studies. Overall, 15 studies specifically developed and/or validated 12 prediction models. Of these, all showed poor discrimination or absent calibration in predicting POAF in externally validated cohorts. CONCLUSIONS: Except for age, reporting of factors associated with POAF is inconsistent and often contradictory. Prediction models have low discrimination, missing calibration statistics, are at risk of bias and show limited clinical applicability. This suggests the need for studies that prospectively collect AF relevant data in large cohorts and then proceed to validate findings in external data sets.

10.
BMC Res Notes ; 14(1): 325, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34429149

RESUMO

OBJECTIVE: We performed a single-center double-blinded, randomized trial to investigate the hemodynamic effects of IV paracetamol in patients with chronic liver disease (CLD) undergoing liver transplantation surgery. Patients with CLD are particularly susceptible to hemodynamic derangements given their low systemic vascular resistance state. Accordingly, hypotension is common in this setting. The hemodynamic effects of IV paracetamol in patients undergoing elective liver transplantation are unknown, therefore we evaluated whether the intraoperative administration of IV paracetamol in patients with chronic liver disease undergoing liver transplantation results in adverse hemodynamic effects. The primary end point was a change in systolic blood pressure 30-min after the preoperative infusion. RESULTS: Twenty-four participants undergoing liver transplantation surgery were randomly assigned to receive a single bolus of IV paracetamol (1 g paracetamol + 3.91 g mannitol per 100 mL) (n = 12) or placebo (0.9% Saline 100 mL) (n = 12). All participants completed their study intervention, and there were no breaches or violations of the trial protocol. Baseline characteristics were similar in both groups. There were no significant differences regarding surgical duration, intraoperative use of fluids, and intraoperative noradrenaline use. After the administration of paracetamol there were no significant differences observed in blood pressure or other hemodynamic parameters when compared to placebo.


Assuntos
Hepatopatias , Transplante de Fígado , Acetaminofen , Hemodinâmica , Humanos , Projetos Piloto
11.
Heart Lung ; 50(6): 870-876, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34403891

RESUMO

BACKGROUND: Crystalloids, 4% albumin and 20% albumin are used for fluid bolus therapy (FBT) in patients after cardiac surgery. However, their detailed early (30 min) hemodynamic effects remain unstudied. METHODS: In a comparative prospective observational trial of 120 ventilated, we studied post cardiac surgery patients who received crystalloid 500 ml FBT, 4% albumin 500 ml FBT or 20% albumin 100 ml FBT (40 per group). We recorded second-by-second hemodynamic parameters and 15-minutely cardiac index (CI) data before and for 30 min after FBT. We compared the crystalloid group (reference) vs. the 4% albumin group, and vs. the 20% albumin group. RESULTS: Immediately after FBT, the mean (standard deviation) CI increase was 0.4 (0.4) L/min/m2 with crystalloids, 0.4 (0.5) L/min/m2 with 4% albumin and 0.3 (0.4) L/min/m2 with 20% albumin, despite the much smaller FBT volume with 20% albumin. Mean arterial pressure (MAP) increase was 11 (10), 12 (9) and 9 (6) mm Hg, respectively. There was no group effect or interaction for changes in CI. However, there were time-group interactions for MAP changes such that crystalloid FBT had faster MAP reduction than 4% (p<0.001) or 20% albumin (p < 0.001). Moreover, patients treated with crystalloid FBT showed a faster decline in central venous pressure, perfusion pressure than the two groups. Finally, 20% albumin attenuated the fall in temperature induced by FBT. CONCLUSION: In postoperative cardiac surgery patients, after a similar initial CI and MAP response, the MAP effect of crystalloid FBT dissipates faster than that of 4% or 20% albumin FBT. These findings can be used to inform clinical practice.

12.
Blood Purif ; : 1-13, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34289471

RESUMO

INTRODUCTION: Higher net ultrafiltration (UFNET) rates are associated with mortality among critically ill patients with acute kidney injury (AKI) and treated with continuous renal replacement therapy (CRRT). OBJECTIVE: The aim of the study was to discover whether UFNET rates are associated with renal recovery and independence from renal replacement therapy (RRT). METHODS: Retrospective cohort study using data from the Randomized Evaluation of Normal versus Augmented Level of Renal Replacement Therapy trial that enrolled 1,433 critically ill patients with AKI and treated with CRRT between December 2005 and November 2008 across 35 intensive care units in Australia and New Zealand. We examined the association between UFNET rate and time to independence from RRT by day 90 using competing risk regression after accounting for mortality. The UFNET rate was defined as the volume of fluid removed per hour adjusted for patient body weight. RESULTS AND CONCLUSIONS: Median age was 67.3 (interquartile range [IQR], 57-76.3) years, 64.4% were male, median Acute Physiology and Chronic Health Evaluation-III score was 100 (IQR, 84-118), and 634 (44.2%) died by day 90. Kidney recovery occurred in 755 patients (52.7%). Using tertiles of UFNET rates, 3 groups were defined: high, >1.75; middle, 1.01-1.75; and low, <1.01 mL/kg/h. Proportion of patients alive and independent of RRT among the groups were 47.8 versus 57.2 versus 53.0%; p = 0.01. Using competing risk regression, higher UFNET rate tertile compared with middle (cause-specific hazard ratio [csHR], 0.79, 95% CI, 0.66-0.95; subdistribution hazard ratio [sHR], 0.80, 95% CI, 0.67-0.97) and lower (csHR, 0.69, 95% CI, 0.56-0.85; sHR, 0.78, 95% CI 0.64-0.95) tertiles were associated with a longer time to independence from RRT. Every 1.0 mL/kg/h increase in rate was associated with a lower probability of kidney recovery (csHR, 0.81, 95% CI, 0.74-0.89; and sHR, 0.87, 95% CI, 0.80-0.95). Using the joint model, longitudinal increases in UFNET rates were also associated with a lower renal recovery (ß = -0.29, p < 0.001). UFNET rates >1.75 mL/kg/h compared with rates 1.01-1.75 and <1.01 mL/kg/h were associated with a longer duration of dependence on RRT. Randomized clinical trials are required to confirm this UFNET rate-outcome relationship.

14.
Anesth Analg ; 133(4): 1036-1047, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34269720

RESUMO

BACKGROUND: The endothelial glycocalyx, a carbohydrate-rich layer coating all endothelial surfaces, plays a fundamental role in the function of microcirculation. The primary aim of this study was to evaluate the feasibility of using dexamethasone and albumin to protect the endothelial glycocalyx in patients undergoing abdominal surgery. Secondary and exploratory outcomes included efficacy and safety. METHODS: We conducted a multicenter, open-label, blinded end point, phase 2, randomized trial. Patients undergoing colorectal, pancreas, or liver surgery were recruited and randomized to receive either intravenous dexamethasone (16 mg) and 20% albumin (100 mL) at induction of anesthesia, then 200 mL of 20% albumin with each subsequent 1000 mL of crystalloid administered (dexamethasone and albumin [Dex-Alb] group), or crystalloid fluid only with no dexamethasone (control group). Feasibility end points included patient recruitment and retention, consent rate, and successful study drug administration. The primary efficacy end point was the measurement of plasma syndecan-1 level on postoperative day (POD) 1, and secondary end points were heparan sulfate levels and inflammatory markers measured at 4 perioperative timepoints. Safety end points included errors in administration of the intervention, hyperglycemia, occurrence of postoperative complications, and patient retention. RESULTS: Seventy-two patients were randomized. All feasibility end points were achievable. There were no statistically significant differences observed in median (interquartile range) syndecan-1 levels on POD 1 (39 ng·mL-1 [20-97] in the Dex-Alb group versus 41 ng·mL-1 [19-84] in the control group; difference in medians -2.1, 95% confidence interval [CI], -13 to 8.6; P = .69). The Dex-Alb group had lower POD 1 heparan sulfate levels (319 ng·mL-1 [161-717] in the Dex-Alb group versus 1422 [670-2430] ng·mL-1 in the control group; difference in medians -1085, 95% CI, -1779 to -391) and C-reactive protein (CRP) levels on POD 1 (48 [29-77] mg·L-1 in the Dex-Alb group versus 85 mg·L-1 [49-133] in the control group; difference in medians -48, 95% CI, -75 to -21). Fewer patients had one or more postoperative complication in the Dex-Alb group than in the control group (6 [17%] vs 18 patients [50%]; odds ratio = 0.2, 95% CI, 0.06-0.6). CONCLUSIONS: Intravenous dexamethasone and albumin administration was feasible but did not reduce syndecan-1 on POD 1 in patients undergoing abdominal surgery. Given the clinically important CIs observed between the groups for heparan sulfate, CRP, and postoperative complications, a larger trial assessing the associations between dexamethasone and albumin administration and these outcomes is warranted.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34261949

RESUMO

OBJECTIVES: To describe the characteristics, hemodynamic, and physiologic changes after 4% albumin fluid boluses in critically ill children. DESIGN: Retrospective observational study. SETTING: Single-center PICU. PATIENTS: Children in a cardiac and general PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between January 2017 and May 2019, there were 1,003 fluid boluses of 4% albumin during 420 of 5,731 admissions (7.8%), most commonly in children with congenital/acquired heart disease (71.2%) and sepsis (7.9%). The median fluid bolus dose was 10 mL/kg (interquartile range, 5.8-14.6 mL/kg), and its duration 30 minutes (interquartile range, 14.0-40.0 min; n = 223). After the fluid bolus, a significant change in mean arterial pressure (2.3 mm Hg [5.1%], 2.7 mm Hg [5.8%], 2.9 mm Hg [6.1%], and 3.8 mm Hg [8.0%] at 1, 2, 3, and 4 hr, respectively [p ≤ 0.001]) only occurred in children less than or equal to 12 months old. A mean arterial pressure response, defined by an increase greater than or equal to 10% from baseline, occurred in 290 of 887 patients (33%) with maximal response at 1 hour. Hypotension at baseline predicted the magnitude of mean arterial pressure increase at 60 (coefficient 24.3 [95% CI, 0.79-7.87]; p = 0.04) and 120 minutes (coefficient 26.1 [95% CI, 2.75-48.2]; p = 0.02). There were no biochemical or hematocrit changes within 4 hours of the fluid bolus. Urine output for the entire cohort was 2 mL/kg/hr at baseline and did not change with the fluid bolus. CONCLUSIONS: Fluid boluses of 4% albumin were common and predominantly in children with cardiac disease and sepsis with a median dose of 10 mL/kg given over half an hour. Such treatment was associated with significant hemodynamic changes only in children less than 12 months old, and we failed to identify an association with urine output.

16.
Aust Crit Care ; 2021 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-34321180

RESUMO

BACKGROUND: Nonurban residential living is associated with adverse outcomes for a number of chronic health conditions. However, it is unclear what effect it has amongst survivors of critical illness. OBJECTIVES: The purpose of this study is to determine whether patients living greater than 50 km from the treating intensive care unit (ICU) have disability outcomes at 6 months that differ from people living within 50 km. METHODS: This was a multicentre, prospective cohort study conducted in five metropolitan ICUs. Participants were adults admitted to the ICU, who received >24 h of mechanical ventilation and survived to hospital discharge. In a secondary analysis of these data, the cohort was dichotomised based on residential distance from the treating ICU: <50 km and ≥50 km. The primary outcome was patient-reported disability using the 12-item World Health Organization's Disability Assessment Schedule (WHODAS 2.0). This was recorded at 6 months after ICU admission by telephone interview. Secondary outcomes included health status as measured by EQ-5D-5L return to work and psychological function as measured by the Hospital Anxiety and Depression Scale (HADS). Multivariable logistic regression was used to assess the association between distance from the ICU and moderate to severe disability, adjusted for potential confounders. Variables included in the multivariable model were deemed to be clinically relevant and had baseline imbalance between groups (p < 0.10). These included marital status and hours of mechanical ventilation. Sensitivity analysis was also conducted using distance in kilometres as a continuous variable. RESULTS: A total of 262 patients were enrolled, and 169 (65%) lived within 50 km of the treating ICU and 93 (35%) lived ≥50 km from the treating ICU (interquartile range [IQR] 10-664 km). There was no difference in patient-reported disability at 6 months between patients living <50 km and those living ≥50 km (WHODAS total disability % [IQR] 10.4 [2.08-25] v 14.6 [2.08-20.8], P = 0.74). There was also no difference between groups for the six major life domains of the WHODAS. There was no difference in rates of anxiety or depression as measured by HADS score (HADS anxiety median [IQR] 4 [1-7] v 3 [1-7], P = 0.60) (HADS depression median [IQR] 3 [1-6] v 3 [1-6], P = 0.62); health status as measured by EQ-5D (mean [SD] 66.7 [20] v 69.8 [22.2], P = 0.24); or health-related unemployment (% (N) 39 [26] v 25 [29.1], P = 0.61). After adjusting for confounders, living ≥50 km from the treating ICU was not associated with increased disability (odds ratio 0.61, 95% confidence interval: 0.33-1.16; P = 0.13) CONCLUSIONS: Survivors of intensive care in Victoria, Australia, who live at least 50 km from the treating ICU did not have greater disability than people living less than 50 km at 6 months after discharge. Living 50 km or more from the treating ICU was not associated with disability, nor was it associated with anxiety or depression, health status, or unemployment due to health.

17.
Crit Care ; 25(1): 250, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34271958

RESUMO

A personalized mechanical ventilation approach for patients with adult respiratory distress syndrome (ARDS) based on lung physiology and morphology, ARDS etiology, lung imaging, and biological phenotypes may improve ventilation practice and outcome. However, additional research is warranted before personalized mechanical ventilation strategies can be applied at the bedside. Ventilatory parameters should be titrated based on close monitoring of targeted physiologic variables and individualized goals. Although low tidal volume (VT) is a standard of care, further individualization of VT may necessitate the evaluation of lung volume reserve (e.g., inspiratory capacity). Low driving pressures provide a target for clinicians to adjust VT and possibly to optimize positive end-expiratory pressure (PEEP), while maintaining plateau pressures below safety thresholds. Esophageal pressure monitoring allows estimation of transpulmonary pressure, but its use requires technical skill and correct physiologic interpretation for clinical application at the bedside. Mechanical power considers ventilatory parameters as a whole in the optimization of ventilation setting, but further studies are necessary to assess its clinical relevance. The identification of recruitability in patients with ARDS is essential to titrate and individualize PEEP. To define gas-exchange targets for individual patients, clinicians should consider issues related to oxygen transport and dead space. In this review, we discuss the rationale for personalized approaches to mechanical ventilation for patients with ARDS, the role of lung imaging, phenotype identification, physiologically based individualized approaches to ventilation, and a future research agenda.

18.
Minerva Anestesiol ; 87(8): 891-902, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34102804

RESUMO

BACKGROUND: COVID-19 is associated with elevated levels of inflammatory cytokines. We present the characteristics and outcomes of patients treated in the Intensive Care Unit (ICU) with immunosuppressive drugs, either tocilizumab or anakinra compared with controls. METHODS: A single-center observational prospective study on ICU invasively ventilated COVID-19 patients. The primary outcome was the clinical improvement at day 28. A Bayesian framework was employed, and all analyses were adjusted for confounders. RESULTS: Sixty-one consecutive invasively ventilated patients were included, nine (14.7%) received tocilizumab and 15 (24.6%) received anakinra. Over the first seven days, tocilizumab was associated with a greater decrease in C-reactive protein (P<0.001). After adjusting for confounders, the probability of clinical improvement at day 28 compared to control was 7∙6% (OR=0.36 [95% CrI: 0.09-1.46]) for tocilizumab and 40.9% (OR=0.89 [95% CrI: 0.32-2.43]) for anakinra. At day 28, the probability of being in a better clinical category was 2.5% (OR=2.98 [95% CrI: 1.00-8.88]) for tocilizumab, and 49.5% (OR=1.00 [95% CrI: 0.42-2.42]) for anakinra. CONCLUSIONS: In invasively ventilated COVID-19 patients, treatment with anakinra was associated with a higher probability of clinical improvement compared to tocilizumab; however, treatment with either drug did not result in clinically meaningful improvements compared with controls.


Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Teorema de Bayes , Humanos , Estudos Prospectivos , Síndrome do Desconforto Respiratório/tratamento farmacológico , SARS-CoV-2 , Resultado do Tratamento
19.
Br J Pharmacol ; 178(19): 3864-3868, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34061355

RESUMO

Sepsis induced by bacteria or viruses can result in multiorgan dysfunction, which is a major cause of death in intensive care units. Current treatments are only supportive, and there are no treatments that reverse the pathophysiological effects of sepsis. Vitamin C has antioxidant, anti-inflammatory, anticoagulant and immune modulatory actions, so it is a rational treatment for sepsis. Here, we summarise data that support the use of megadose vitamin C as a treatment for sepsis and COVID-19. Megadose intravenous sodium ascorbate (150 g per 40 kg over 7 h) dramatically improved the clinical state and cardiovascular, pulmonary, hepatic and renal function and decreased body temperature, in a clinically relevant ovine model of Gram-negative bacteria-induced sepsis. In a critically ill COVID-19 patient, intravenous sodium ascorbate (60 g) restored arterial pressure, improved renal function and increased arterial blood oxygen levels. These findings suggest that megadose vitamin C should be trialled as a treatment for sepsis and COVID-19.


Assuntos
COVID-19 , Sepse , Animais , Ácido Ascórbico , Humanos , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , SARS-CoV-2 , Sepse/tratamento farmacológico , Ovinos
20.
J Crit Care ; 65: 116-123, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34118502

RESUMO

PURPOSE: To investigate the association between sex and illness severity and mortality of ICU patients. METHODS: We performed systematic searches of MEDLINE and EMBASE for observational studies of adult ICU patients that explicitly examined the association between sex and illness severity or mortality. We used a random effects model to calculate standardised mean differences in illness severity scores and pooled odds ratios for mortality of women compared to men. RESULTS: We identified 21 studies with 505,138 participants in total (43.1% women). There was substantial heterogeneity among studies. Only two studies were at low risk of bias overall. At ICU admission, there was a pattern of higher illness severity scores among women (standardised mean difference 0.04, 95% CI -0.01-0.09). Women had higher risk-adjusted mortality than men at ICU discharge (OR 1.25 95% CI 1.03-1.50) and 1 year (OR 1.08, 95% CI 1.02-1.13), however this finding was not robust to sensitivity analysis. CONCLUSIONS: Women tend to have higher illness severity scores at ICU admission. Women also appear to have higher risk-adjusted mortality than men at ICU discharge and at 1 year. Given the heterogeneity and risk of bias in the existing literature, additional studies are needed to confirm or refute these findings.

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