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Alimentary Pharmacology & Therapeutics Oct 2022Previous studies suggested increased mortality in patients with hepatorenal syndrome type 1 (HRS1) and advanced acute-on-chronic liver failure (ACLF). (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Previous studies suggested increased mortality in patients with hepatorenal syndrome type 1 (HRS1) and advanced acute-on-chronic liver failure (ACLF).
AIM
To assess mortality and respiratory failure (RF) in patients with HRS1 and ACLF treated with terlipressin.
METHODS
In the CONFIRM study, we randomised 299 patients with HRS1 2:1 to terlipressin or placebo, both with albumin. At enrolment, all patients were assessed for organ failure (OF) using a validated ACLF grading system. Post hoc analyses assessed the effects of terlipressin vs. placebo on the incidence of RF and 90-day mortality.
RESULTS
The incidence of RF with terlipressin (n = 200) was 9.4% in patients with grades 1-2 ACLF, and 30% with grade 3 ACLF (p = 0.0002); no such difference was observed in placebo-treated patients (n = 99) (6.2% grades 1-2 vs. 0% grade 3 ACLF, p > 0.05). RF incidence between terlipressin and placebo in patients with grade 3 ACLF was significant (p = 0.01). Baseline predictors of RF with terlipressin were INR (p = 0.011), mean arterial pressure (p = 0.037), and SpO (p = 0.014). Prior albumin as a continuous variable was not a predictor of RF. 90-day survival between terlipressin and placebo arms was similar for grades 1-2 ACLF (55.5% and 56.6%, respectively), but lower for grade 3 ACLF (27.55% vs. 50.0%) (p = 0.122), mainly related to RF.
CONCLUSION
Terlipressin should be used with caution in patients with HRS1 and grade 3 ACLF. Patients with hypoxaemia are at increased risk of RF and mortality.
Topics: Acute-On-Chronic Liver Failure; Albumins; Hepatorenal Syndrome; Humans; Liver Cirrhosis; Lypressin; Respiratory Insufficiency; Terlipressin; Vasoconstrictor Agents
PubMed: 35995728
DOI: 10.1111/apt.17195 -
Critical Care (London, England) Feb 2020Optimal timing for the start of vasopressors (VP) in septic shock has not been widely studied since it is assumed that fluids must be administered in advance. We sought... (Clinical Trial)
Clinical Trial
BACKGROUND
Optimal timing for the start of vasopressors (VP) in septic shock has not been widely studied since it is assumed that fluids must be administered in advance. We sought to evaluate whether a very early start of VP, even without completing the initial fluid loading, might impact clinical outcomes in septic shock.
METHODS
A total of 337 patients with sepsis requiring VP support for at least 6 h were initially selected from a prospectively collected database in a 90-bed mixed-ICU during a 24-month period. They were classified into very-early (VE-VPs) or delayed vasopressor start (D-VPs) categories according to whether norepinephrine was initiated or not within/before the next hour of the first resuscitative fluid load. Then, VE-VPs (n = 93) patients were 1:1 propensity matched to D-VPs (n = 93) based on age; source of admission (emergency room, general wards, intensive care unit); chronic and acute comorbidities; and lactate, heart rate, systolic, and diastolic pressure at vasopressor start. A risk-adjusted Cox proportional hazard model was fitted to assess the association between VE-VPs and day 28 mortality. Finally, a sensitivity analysis was performed also including those patients requiring VP support for less than 6 h.
RESULTS
Patients subjected to VE-VPs received significantly less resuscitation fluids at vasopressor starting (0[0-510] vs. 1500[650-2300] mL, p < 0.001) and during the first 8 h of resuscitation (1100[500-1900] vs. 2600[1600-3800] mL, p < 0.001), with no significant increase in acute renal failure and/or renal replacement therapy requirements. VE-VPs was related with significant lower net fluid balances 8 and 24 h after VPs. VE-VPs was also associated with a significant reduction in the risk of death compared to D-VPs (HR 0.31, CI95% 0.17-0.57, p < 0.001) at day 28. Such association was maintained after including patients receiving vasopressors for < 6 h.
CONCLUSION
A very early start of vasopressor support seems to be safe, might limit the amount of fluids to resuscitate septic shock, and could lead to better clinical outcomes.
Topics: Acute Kidney Injury; Aged; Female; Fluid Therapy; Humans; Intensive Care Units; Male; Middle Aged; Norepinephrine; Renal Replacement Therapy; Shock, Septic; Time Factors; Vasoconstrictor Agents
PubMed: 32059682
DOI: 10.1186/s13054-020-2756-3 -
Critical Care (London, England) Jul 2020Measurement of central venous pressure (CVP) can be a useful clinical tool. However, the formal utility of CVP measurement in preventing mortality in septic patients has...
PURPOSE
Measurement of central venous pressure (CVP) can be a useful clinical tool. However, the formal utility of CVP measurement in preventing mortality in septic patients has never been proven.
METHODS
The Medical Information Mart for Intensive Care III (MIMIC-III) database was searched to identify septic patients with and without CVP measurements. The primary outcome was 28-day mortality. Multivariate regression was used to elucidate the relationship between CVP measurement and 28-day mortality, and propensity score matching (PSM) and an inverse probability of treatment weighing (IPTW) were employed to validate our findings.
RESULTS
A total of 10,275 patients were included in our study, of which 4516 patients (44%) underwent CVP measurement within 24 h of intensive care unit (ICU) admission. The risk of 28-day mortality was reduced in the CVP group (OR 0.60 (95% CI 0.51-0.70; p < 0.001)). Patients in the CVP group received more fluid on day 1 and had a shorter duration of mechanical ventilation and vasopressor use, and the reduction in serum lactate was greater than that in the no CVP group. The mediating effect of serum lactate reduction was significant for the whole cohort (p = 0.04 for the average causal mediation effect (ACME)) and patients in the CVP group with an initial CVP level below 8 mmHg (p = 0.04 for the ACME).
CONCLUSION
CVP measurement was associated with decreased risk-adjusted 28-day mortality among patients with sepsis and was proportionally mediated through serum lactate reduction.
Topics: Aged; Aged, 80 and over; Central Venous Pressure; Cohort Studies; Databases, Factual; Female; Fluid Therapy; Humans; Intensive Care Units; Male; Middle Aged; Monitoring, Physiologic; Outcome Assessment, Health Care; Prognosis; Retrospective Studies; Sepsis; Vasoconstrictor Agents
PubMed: 32665010
DOI: 10.1186/s13054-020-03109-9 -
BMC Infectious Diseases Apr 2023vasopressin is commonly used as a second-line vasopressor for patients with septic shock, but the optimal timing of initiation is uncertain. This study was designed to... (Observational Study)
Observational Study
BACKGROUND
vasopressin is commonly used as a second-line vasopressor for patients with septic shock, but the optimal timing of initiation is uncertain. This study was designed to investigate when vasopressin initiation may be beneficial for 28-day mortality in septic shock patients.
METHODS
This was a retrospective observational cohort study from the MIMIC-III v1.4 and MIMIC-IV v2.0 databases. All adults diagnosed with septic shock according to Sepsis-3 criteria were included. Patients were stratified into two groups based on norepinephrine (NE) dose at the time of vasopressin initiation, defined as the low doses of NE group (NE<0.25 µg/kg/min) and the high doses of NE group (NE ≥ 0.25 µg/kg/min). The primary end-point was 28-day mortality after diagnosis of septic shock. The analysis involved propensity score matching (PSM), multivariable logistic regression, doubly robust estimation, the gradient boosted model, and an inverse probability-weighting model.
RESULTS
A total of 1817 eligible patients were included in our original cohort (613 in the low doses of NE group and 1204 in the high doses of NE group). After 1:1 PSM, 535 patients from each group with no difference in disease severity were included in the analysis. The results showed that vasopressin initiation at low doses of NE was associated with reduced 28-day mortality (odds ratio [OR] 0.660, 95% confidence interval [CI] 0.518-0.840, p < 0.001). Compared with patients in the high doses of NE group, patients in the low doses of NE group received significantly shorter duration of NE, with less intravenous fluid volume on the first day after initiation of vasopressin, more urine on the second day, and longer mechanical ventilation-free days and CRRT-free days. Nevertheless, there were no significant differences in hemodynamic response to vasopressin, duration of vasopressin, and ICU or hospital length of stay.
CONCLUSIONS
Among adults with septic shock, vasopressin initiation when low-dose NE was used was associated with an improvement in 28-day mortality.
Topics: Adult; Humans; Shock, Septic; Cohort Studies; Vasoconstrictor Agents; Vasopressins; Norepinephrine; Retrospective Studies
PubMed: 37013474
DOI: 10.1186/s12879-023-08147-6 -
Critical Care (London, England) Aug 2023During septic shock, vasopressor infusion is usually started only after having corrected the hypovolaemic component of circulatory failure, even in the most severe...
During septic shock, vasopressor infusion is usually started only after having corrected the hypovolaemic component of circulatory failure, even in the most severe patients. However, earlier administration of norepinephrine, simultaneously with fluid resuscitation, should be considered in some cases. Duration and depth of hypotension strongly worsen outcomes in septic shock patients. However, the response of arterial pressure to volume expansion is inconstant, delayed, and transitory. In the case of profound, life-threatening hypotension, relying only on fluids to restore blood pressure may unduly prolong hypotension and organ hypoperfusion. Conversely, norepinephrine rapidly increases and better stabilizes arterial pressure. By binding venous adrenergic receptors, it transforms part of the unstressed blood volume into stressed blood volume. It increases the mean systemic filling pressure and increases the fluid-induced increase in mean systemic filling pressure, as observed in septic shock patients. This may improve end-organ perfusion, as shown by some animal studies. Two observational studies comparing early vs. later administration of norepinephrine in septic shock patients using a propensity score showed that early administration reduced the administered fluid volume and day-28 mortality. Conversely, in another propensity score-based study, norepinephrine administration within the first hour following shock diagnosis increased day-28 mortality. The only randomized controlled study that compared the early administration of norepinephrine alone to a placebo showed that the early continuous administration of norepinephrine at a fixed dose of 0.05 µg/kg/min, with norepinephrine added in open label, showed that shock control was achieved more often than in the placebo group. The choice of starting norepinephrine administration early should be adapted to the patient's condition. Logically, it should first be addressed to patients with profound hypotension, when the arterial tone is very low, as suggested by a low diastolic blood pressure (e.g. ≤ 40 mmHg), or by a high diastolic shock index (heart rate/diastolic blood pressure) (e.g. ≥ 3). Early administration of norepinephrine should also be considered in patients in whom fluid accumulation is likely to occur or in whom fluid accumulation would be particularly deleterious (in case of acute respiratory distress syndrome or intra-abdominal hypertension for example).
Topics: Animals; Blood Pressure; Hypotension; Norepinephrine; Shock, Septic; Vasoconstrictor Agents; Humans
PubMed: 37608327
DOI: 10.1186/s13054-023-04593-5 -
British Journal of Anaesthesia Sep 2022Chiu and colleagues report a retrospective analysis describing the 5-yr trend in both intraoperative fluid and vasopressor administration in 32 250 patients undergoing...
Chiu and colleagues report a retrospective analysis describing the 5-yr trend in both intraoperative fluid and vasopressor administration in 32 250 patients undergoing elective abdominal surgery within the Multicenter Perioperative Outcomes Group (MPOG) database from 2015 to 2019, and exploring the association between these two factors and acute kidney injury. Modelling predicted the lowest risk for acute kidney injury when the administered crystalloid volume was 15-20 ml kg h, and an 80% increase in risk for acute kidney injury as intraoperative vasopressor use increased from 0 to 0.04 μg kg min of norepinephrine equivalents. Although these results are consistent with those of a large, randomised trial (REstrictive Versus LIbEral Fluid Therapy in Major Abdominal Surgery [RELIEF]) published in 2018, the mean intraoperative volume of crystalloid administered in the current study declined monotonically through every year included, from 6.4 ml kg h in 2015 to 5.5 ml kg h in 2019. These new findings support the broad generalisability of the RELIEF trial; highlight the complexity of the relationship between intravenous crystalloid volume infused, arterial pressure, and acute kidney injury; and demonstrate the ongoing challenge of translating high-quality evidence into clinical practice.
Topics: Abdomen; Acute Kidney Injury; Crystalloid Solutions; Fluid Therapy; Humans; Retrospective Studies; Vasoconstrictor Agents
PubMed: 35927095
DOI: 10.1016/j.bja.2022.06.016 -
Clinical Journal of the American... Jun 2022The definition of sepsis has evolved significantly over the past three decades. Today, sepsis is defined as a dysregulated host immune response to microbial invasion... (Review)
Review
The definition of sepsis has evolved significantly over the past three decades. Today, sepsis is defined as a dysregulated host immune response to microbial invasion leading to end organ dysfunction. Septic shock is characterized by hypotension requiring vasopressors after adequate fluid resuscitation with elevated lactate. Early recognition and intervention remain hallmarks for sepsis management. We addressed the current literature and assimilated thought regarding optimum initial resuscitation of the patient with sepsis. A nuanced understanding of the physiology of lactate is provided in our review. Physiologic and practical knowledge of steroid and vasopressor therapy for sepsis is crucial and addressed. As blood purification may interest the nephrologist treating sepsis, we have also added a brief discussion of its status.
Topics: Fluid Therapy; Humans; Lactic Acid; Nephrologists; Sepsis; Shock, Septic; Vasoconstrictor Agents
PubMed: 35551069
DOI: 10.2215/CJN.14381121 -
Critical Care (London, England) Jul 2023Albumin infusion is the primary therapeutic strategy for septic patients with liver cirrhosis. Although recent studies have investigated the efficacy of albumin in the...
BACKGROUND
Albumin infusion is the primary therapeutic strategy for septic patients with liver cirrhosis. Although recent studies have investigated the efficacy of albumin in the resuscitation stage of septic patients with liver cirrhosis, it remains unclear whether daily albumin administration can improve outcomes. Furthermore, the indications for initiating albumin therapy are not well defined.
METHODS
Septic patients with liver cirrhosis were obtained from the Medical Information Mart for Intensive Care (MIMIC-IV 2.0) database. Marginal structural Cox models were employed to investigate the association between daily albumin infusion and 28-day mortality. We also aimed to explore under what circumstances enrolled patients could benefit most from albumin administration, based on the clinical parameters collected on the day of albumin infusion, including serum albumin concentration, serum lactate concentration, mean arterial pressure (MAP), and vasopressor dosage.
RESULTS
A total of 2265 patients were included in the final analysis, of whom 1093 (48.3%) had received albumin treatment at least once. The overall 28-day mortality was 29.6%. After marginal structural modeling, daily albumin infusion was associated with a reduced risk of 28-day death (hazard ratio, 0.76; 95% CI 0.61-0.94). We found that patients benefit most from albumin infusion when initiated on the day of serum albumin concentration between 2.5 and 3.0 g/dL, serum lactate concentration greater than or equal to 2 mmol/L, MAP less than 60 mmHg, or vasopressor dosage between 0.2 and 0.3 mcg/kg/min (norepinephrine equivalent, NEE).
CONCLUSIONS
Albumin infusion is associated with a reduction in mortality in septic patients with liver cirrhosis under specific circumstances. Serum albumin concentration, serum lactate, MAP, and vasopressor dosage were found to be modifiers of treatment effectiveness and should be considered when deciding to initial albumin infusion.
Topics: Humans; Shock, Septic; Vasoconstrictor Agents; Lactic Acid; Liver Cirrhosis; Serum Albumin
PubMed: 37507790
DOI: 10.1186/s13054-023-04587-3 -
Critical Care (London, England) May 2023High dose vasopressors portend poor outcome in vasodilatory shock. We aimed to evaluate the impact of baseline vasopressor dose on outcomes in patients treated with... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
High dose vasopressors portend poor outcome in vasodilatory shock. We aimed to evaluate the impact of baseline vasopressor dose on outcomes in patients treated with angiotensin II (AT II).
METHODS
Exploratory post-hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) trial data. The ATHOS-3 trial randomized 321 patients with vasodilatory shock, who remained hypotensive (mean arterial pressure of 55-70 mmHg) despite receiving standard of care vasopressor support at a norepinephrine-equivalent dose (NED) > 0.2 µg/kg/min, to receive AT II or placebo, both in addition to standard of care vasopressors. Patients were grouped into low (≤ 0.25 µg/kg/min; n = 104) or high (> 0.25 µg/kg/min; n = 217) NED at the time of study drug initiation. The primary outcome was the difference in 28-day survival between the AT II and placebo subgroups in those with a baseline NED ≤ 0.25 µg/kg/min at the time of study drug initiation.
RESULTS
Of 321 patients, the median baseline NED in the low-NED subgroup was similar in the AT II (n = 56) and placebo (n = 48) groups (median of each arm 0.21 µg/kg/min, p = 0.45). In the high-NED subgroup, the median baseline NEDs were also similar (0.47 µg/kg/min AT II group, n = 107 vs. 0.45 µg/kg/min placebo group, n = 110, p = 0.75). After adjusting for severity of illness, those randomized to AT II in the low-NED subgroup were half as likely to die at 28-days compared to placebo (HR 0.509; 95% CI 0.274-0.945, p = 0.03). No differences in 28-day survival between AT II and placebo groups were found in the high-NED subgroup (HR 0.933; 95% CI 0.644-1.350, p = 0.71). Serious adverse events were less frequent in the low-NED AT II subgroup compared to the placebo low-NED subgroup, though differences were not statistically significant, and were comparable in the high-NED subgroups.
CONCLUSIONS
This exploratory post-hoc analysis of phase 3 clinical trial data suggests a potential benefit of AT II introduction at lower doses of other vasopressor agents. These data may inform design of a prospective trial.
TRIAL REGISTRATION
The ATHOS-3 trial was registered in the clinicaltrials.gov repository (no. NCT02338843). Registered 14 January 2015.
Topics: Humans; Angiotensin II; Hypotension; Norepinephrine; Prospective Studies; Shock; Vasoconstrictor Agents
PubMed: 37147690
DOI: 10.1186/s13054-023-04446-1 -
Critical Care (London, England) Apr 2021It is unclear whether vasopressors can be safely administered through a peripheral intravenous (PIV). Systematic review and meta-analysis methodology was used to examine... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It is unclear whether vasopressors can be safely administered through a peripheral intravenous (PIV). Systematic review and meta-analysis methodology was used to examine the incidence of local anatomic adverse events associated with PIV vasopressor administration in patients of any age cared for in any acute care environment.
METHODS
MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of controlled trials, and the Database of Abstracts of Reviews of Effects were searched without restriction from inception to October 2019. References of included studies and related reviews, as well as relevant conference proceedings were also searched. Studies were included if they were: (1) cohort, quasi-experimental, or randomized controlled trial study design; (2) conducted in humans of any age or clinical setting; and (3) reported on local anatomic adverse events associated with PIV vasopressor administration. Risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomized trials or the Joanna Briggs Institute checklist for prevalence studies where appropriate. Incidence estimates were pooled using random effects meta-analysis. Subgroup analyses were used to explore sources of heterogeneity.
RESULTS
Twenty-three studies were included in the systematic review, of which 16 and 7 described adults and children, respectively. Meta-analysis from 11 adult studies including 16,055 patients demonstrated a pooled incidence proportion of adverse events associated with PIV vasopressor administration as 1.8% (95% CI 0.1-4.8%, I = 93.7%). In children, meta-analysis from four studies and 388 patients demonstrated a pooled incidence proportion of adverse events as 3.3% (95% CI 0.0-10.1%, I = 82.4%). Subgroup analyses did not detect any statistically significant effects associated with stratification based on differences in clinical location, risk of bias or design between studies, PIV location and size, or vasopressor type or duration. Most studies had high or some concern for risk of bias.
CONCLUSION
The incidence of adverse events associated with PIV vasopressor administration is low. Additional research is required to examine the effects of PIV location and size, vasopressor type and dose, and patient characteristics on the safety of PIV vasopressor administration.
Topics: Catheterization, Peripheral; Drug-Related Side Effects and Adverse Reactions; Humans; Vasoconstrictor Agents
PubMed: 33863361
DOI: 10.1186/s13054-021-03553-1