Hydrochlorothiazide in intensive care unit-acquired hypernatremia: A randomized controlled trial.

PURPOSE: Thiazides are suggested as a treatment for intensive care unit (ICU)-acquired hypernatremia (IAH). The primary aim of the study was reducing serum sodium concentration (sNa) in patients with IAH with hydrochlorothiazide (HCT) in comparison to placebo. Secondary end points were a difference in urine sodium concentration (uNa) and duration of severe IAH. MATERIALS: A monocentric, double-blind, placebo-controlled trial was conducted in 50 patients with IAH and urine potassium + uNa less than sNa in a spot urine sample. Patients were randomized to HCT 25 mg or placebo 1 qd for maximal 7 days. Patients on renal replacement therapy, on medication inducing diabetes insipidus, or with recent use of diuretics were excluded. IAH was defined as sNa of at least 143 mmol/L. RESULTS: At baseline, sNa and uNa were comparable between groups. During the study period, sNa decreased significantly with median 4 mmol/L in both groups, with no significant difference between groups (P=.32). Median uNa increased significantly in both groups (46 [16-86] mmol/L in the HCT-group; 20 [10-66]mmol/L in the placebo group), with no difference between groups (P=.34). Median duration of sNa of at least 145 mmol/L was 3 days in both groups (P=.91). CONCLUSION: HCT 25 mg 1 qd did not significantly affect sNa or uNa in patients with IAH.

Plasma glutamine levels in patients after non-elective or elective ICU admission: an observational study.

BACKGROUND: A low plasma glutamine level at the time of acute admission to the intensive care unit (ICU) is an independent predictor of an unfavourable outcome in critically ill patients. The primary objective of this study was to determine whether there are differences in plasma glutamine levels upon non-elective or elective ICU admission. The secondary objective was to compare glutamine levels over time, and to determine correlations between glutamine levels and the severity of illness and presence of infection in ICU patients. METHODS: We performed a single-centre observational study in a closed-format, 22-bed, mixed ICU. Plasma glutamine levels were measured at admission and every morning at 6.00 a.m. during the ICU stay. We aimed to include at least 80 patients per group. The study was approved by the local Medical Ethics Committee. RESULTS: In 88 patients after elective surgery, the median plasma glutamine level at admission was significantly higher compared with that in 90 non-elective patients (0.43 mmol/l [0.33-0.55 mmol/l] versus 0.25 mmol/l [0.09-0.37 mmol/l], P = 0.001). During the ICU stay, plasma glutamine levels remained significantly higher in elective patients than in non-elective patients. There was a significant correlation between the APACHE IV score and glutamine levels (R = 0.52, P < 0.001). Moreover, backward linear regression analysis showed that this correlation was independently associated with the APACHE IV score and the presence of infection, but not with the type of admission. CONCLUSIONS: Plasma glutamine levels are significantly lower after non-elective admission compared with elective admission to the ICU. A considerable amount of elective and non-elective patients have decreased plasma glutamine levels, but this is not independently associated with the type of admission. In contrast to previous studies, we found that plasma glutamine levels were determined by the severity of illness and the presence of an infection. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT02310035.

Elevated C-reactive protein levels at ICU discharge as a predictor of ICU outcome: a retrospective cohort study.

BACKGROUND: Before discharging a patient from the ICU, an adequate patient evaluation is needed to detect individuals as high risk for unfavorable outcome. A pro- or anti-inflammatory status is a potential risk factor for an adverse outcome, and elevated CRP concentrations have shown to correlate with organ failure. Several studies have been performed to evaluate the use of CRP as a marker of post-ICU prognosis. Results are seemingly conflicting, and it is worthwhile to investigate these markers further as CRP is an adequate marker of pro- and anti-inflammatory status of the patient. We aimed to test the hypothesis that elevated CRP levels at ICU discharge are associated with an increased risk of ICU readmission and in-hospital mortality in patients with a prolonged ICU stay. METHODS: A retrospective cohort study was performed in a single-center hospital with an 18-bed mixed medical/surgical ICU. Patients discharged alive from the ICU with at least 48-h ICU length of stay were evaluated. Patients were distributed into two groups: 'high CRP' (≥75 mg/L) and 'low CRP' (<75 mg/L) at ICU discharge. We assessed the difference in adverse outcome (ICU readmission and/or in-hospital mortality) between these groups. RESULTS: A total of 998 patients were included. Compared to the 'low CRP' group, patients in the 'high CRP' group had a higher readmission rate (13.1 vs. 7.4 %; p = 0.003). The post-ICU mortality rate in the 'high CRP' group and 'low CRP' group was 6.9 % and 4.7 %, respectively; p = 0.127. Combined readmission and mortality rates were significantly higher in the 'high CRP' group in comparison with the 'low CRP' group (17.9 vs. 10.1 %; p = 0.001). Hospital mortality in patients readmitted to the ICU was significantly higher than in non-readmitted patients (20 vs. 4.3 %; p < 0.001). Strikingly, the 'high CRP' group had significantly lower APACHE II and SOFA scores at ICU admission compared to the 'low CRP' group. This highlights the potential for ICU-acquired risk factors, including CRP. CONCLUSIONS: A high CRP concentration (≥75 mg/L) within 24 h before ICU discharge is associated with an increased risk of adverse outcome post-ICU discharge. However, CRP at discharge represents only a very moderate risk factor and may not be used for individual clinical decision-making.

'Sepsis-related anemia' is absent at hospital presentation; a retrospective cohort analysis.

BACKGROUND: Anemia is a common feature during sepsis that occurs due to iatrogenic blood loss, depression of serum iron levels and erythropoietin production, and a decreased lifespan of erythrocytes. However, these mechanisms are unlikely to play a role in anemia at the start of sepsis. Moreover, sequestration of fluids, renal failure and increase of intravascular space may additionally influence the change in hemoglobin concentration during intravenous fluid administration in the acute phase of sepsis. METHODS: In this retrospective study, patients who were admitted acutely to the Intensive Care Unit (ICU) were included. Patients who fulfilled the international criteria for severe sepsis or septic shock were included in the sepsis group (S-group). The remaining patients were allocated to the control group (C-group). Laboratory data from blood samples taken at first presentation to the hospital and at admission to the ICU, the amount of intravenous fluid administration and length of stay in the emergency department were collected and tested for significant differences between groups. RESULTS: The difference in hemoglobin concentration between the S-group (n = 296) and C-group (n = 320) at first presentation in hospital was not significant (8.8 ± 1.2 versus 8.9 ± 1.2 mmol/l, respectively, p = 0.07). The reduction in hemoglobin concentration from the first presentation at the emergency department to ICU admission was significantly greater in the S-group compared to the C-group (1 [0.5-1.7] versus 0.5 [0.1-1.1] mmol/l, (p < 0.001)). Spearman rho correlation coefficients between the reduction in hemoglobin concentration and the amount of intravenous fluids administered or the creatinine level in the emergency department were significant (0.3 and 0.4, respectively, p < 0.001). In a multivariate regression analysis, creatinine, the amount of fluid administration and the presence of sepsis remained independently associated. CONCLUSIONS: Prior to in-hospital intravenous fluid administration, there is no significant difference in hemoglobin concentration between acute septic patients and acutely ill controls. Within several hours after hospital admission, there is a significant reduction in hemoglobin concentration, not only associated with the amount of intravenous fluids administered and the creatinine level, but also independently with sepsis itself.

The impact of a pulmonary-artery-catheter-based protocol on fluid and catecholamine administration in early sepsis.

Objective. The pulmonary artery catheter (PAC) remains topic of debate. Despite abundant data, it is of note that many trials did not incorporate a treatment protocol. Methods. We retrospectively evaluated fluid balances and catecholamine doses in septic patients after the introduction of a PAC-based treatment protocol in comparison to historic controls. Results. 2 × 70 patients were included. The first day the PAC group had a significantly higher positive fluid balance in comparison to controls (6.1 ± 2.6 versus 3.8 ± 2.4 litre, P < 0.001). After 7 days the cumulative fluid balance in the PAC group was significantly lower than in controls (9.4 ± 7.4 versus 13 ± 7.6 litre, P = 0.001). Maximum dose of norepinephrine was significantly higher in the PAC group. Compared to controls this was associated with a significant reduction in ventilator and ICU days. Conclusions. Introduction of a PAC-based treatment protocol in sepsis changed the administration of fluid and vasopressors significantly.

Effects of nitroglycerin on sublingual microcirculatory blood flow in patients with severe sepsis/septic shock after a strict resuscitation protocol: a double-blind randomized placebo controlled trial.

OBJECTIVES: Microcirculatory alterations have been associated with morbidity and mortality in human sepsis. Such alterations occur despite pressure-guided resuscitation. Earlier data suggested that impaired microcirculatory blood flow could be corrected with intravenous nitroglycerin in these patients. We tested this concept after fulfillment of preset systemic hemodynamic resuscitation end points in the early phase of sepsis. DESIGN: Prospective, single center, randomized, placebo-controlled, double-blind clinical trial. SETTING: Closed-format 22-bed mixed intensive care unit in a tertiary teaching hospital. PATIENTS: Patients > or =18 yrs with sepsis, according to international criteria, and at least one early sign of organ dysfunction, as the principal reason for intensive care unit admission, were eligible for enrollment. INTERVENTIONS: Patients were randomly assigned to receive nitroglycerin (n = 35) or placebo (n = 35) after fulfillment of protocol-driven resuscitation end points. This trial is registered with ClinicalTrials.gov as NCT00493415. MEASUREMENTS AND MAIN RESULTS: Primary outcome was sublingual microcirculatory blood flow of small vessels, as assessed by side-stream dark field imaging. After protocolized resuscitation, we observed recruitment of sublingual microcirculation in both groups, as indicated by a significant improvement in the microcirculatory flow index after 24 hrs, in comparison to baseline. However, no difference in the sublingual microvascular flow index was observed between groups. The median microvascular flow index in sublingual small-sized vessels was 2.71 (1.85-3) in the nitroglycerin group and 2.71 (1.27-3), p = .80, in the placebo group. In medium-sized vessels, the respective values were 3 (2.75-3) vs. 2.86 (2.19-3), p = .21, and in large-sized vessels, 3 (3-3) vs. 3 (2.89-3), p = .06. In-hospital mortality, as a secondary outcome, was 34.3% in the nitroglycerin group and 14.2% in the placebo group, p = .09. CONCLUSIONS: In the context of a strict resuscitation protocol, based upon fulfillment of systemic hemodynamic end points in patients with early-phase severe sepsis or septic shock, we conclude that intravenous nitroglycerin does not promote sublingual microcirculatory blood flow.

Furosemide does not improve renal recovery after hemofiltration for acute renal failure in critically ill patients: a double blind randomized controlled trial.

OBJECTIVE: To study the potential beneficial role of furosemide in resolving renal failure after hemofiltration in mechanically ventilated critically ill patients. DESIGN: Single-center randomized, double blind, placebo-controlled study. SETTING: A 13-bed mixed intensive care unit (ICU) in a teaching hospital. PATIENTS: Patients who had been treated with continuous venovenous hemofiltration were included. INTERVENTIONS: After the end of continuous venovenous hemofiltration, the urine of the first 4 hours was collected for measuring creatinine clearance. Patients were subsequently randomized for furosemide (0.5 mg/kg/hr) or placebo by continuous infusion. To prevent hypovolemia, the rate of fluid infusion was adapted every hour and was set as the urinary production of the previous hour. MEASUREMENTS AND MAIN RESULTS: End points were renal recovery (creatinine clearance more than 30 mL/min or stable serum creatinine without renal replacement therapy) in the ICU and in the hospital. Seventy-two patients were included and 71 were eligible for the analysis. The 36 furosemide-treated patients had a significantly increased urinary volume compared with the 35 placebo-treated patients (median 247 mL/hr (interquartile range [IQR] 774 mL/hr) vs. 117 mL/hr (IQR 158 mL/hr), p = 0.003) and greater sodium excretion (median 73 mmol/L (IQR 48) vs. 37 (IQR 48) mmol/L, p = 0.001). In the furosemide group 25 patients and in the placebo group 27 patients showed recovery of renal function at ICU discharge (p = 0.46). Two patients of the furosemide group needed long-term dialysis dependency (p = 0.23). CONCLUSION: Furosemide by continuous infusion in the recovery phase of hemofiltration-dependent acute kidney failure did increase urinary volume and sodium excretion but did not lead to a shorter duration of renal failure or more frequent renal recovery.

Disparity between skin perfusion and sublingual microcirculatory alterations in severe sepsis and septic shock: a prospective observational study.

OBJECTIVE: Measurement of central-to-toe temperature difference has been advocated as an index of severity of shock and as a guide for circulatory therapy in critically ill patients. However, septic shock, in contrast to other forms of shock, is associated with a distributive malfunction resulting in a disparity between vascular compartments. Although this disparity has been established between systemic and microcirculatory parameters, it is unclear whether such disparity exists between skin perfusion and microcirculation. To test this hypothesis of disparity, we simultaneously measured parameters of the two vascular compartments, in the early phase of sepsis. DESIGN: Prospective observational study in patients with severe sepsis/septic shock in the first 6 h of ICU admission. Simultaneous measurements of central-to-toe temperature difference and sublingual microcirculatory orthogonal polarization spectral imaging, together with parameters of systemic hemodynamics. SETTING: 22 bed mixed-ICU in a tertiary teaching hospital. PATIENTS: 35 consecutive patients in a 12-month period. MEASUREMENTS AND RESULTS: In 35 septic patients and a median APACHE II score of 20, no correlation between central-to-toe temperature gradient and microvascular flow index was observed (r (s) = -0.08, p =0.65). Also no significant correlation between temperature gradient/microvascular flow index and systemic hemodynamic parameters could be demonstrated. CONCLUSIONS: During the early phase of resuscitated severe sepsis and septic shock there appears to be no correlation between sublingual microcirculatory alterations and the central-to-toe temperature difference. This finding adds to the concept of a dispersive nature of blood flow under conditions of sepsis between microcirculatory and systemic hemodynamics.

An observational study on the effects of nadroparin-based and citrate-based continuous venovenous hemofiltration on calcium metabolism.

BACKGROUND: To study calcium homeostasis during citrate-based compared to nadroparin-based CVVH in critically-ill patients with acute renal failure. METHODS: 11 patients were observed during citrate anticoagulation, 9 with nadroparin and 10 controls. Citrate was chosen for patients with active or at risk for bleeding. RESULTS: The controls had, at 24 h, a median serum iCa of 1.1 mmol/l, the citrate group 0.87 mmol/l and the nadroparin group 1.1 mmol/l (citrate vs. control p = 0.001, citrate vs. nadroparin p = 0.002). At 48 h, iCa was not significantly different anymore. Ca balance was negative for the citrate group in contrast to the nadroparin group (p = 0.012). Median serum PTH was higher (30.0 pmol/l vs. 6.5 pmol/l, p = 0.003) in the citrate group. CONCLUSION: With a relative low target-serum-iCa (0.8-0.9 mmol/l) citrate CVVH-treated patients had a negative daily calcium balance and a temporarily lower iCa level resulting in an enhanced PTH response in comparison to nadroparin.