Effects of goal-directed crystalloid vs. colloid fluid therapy on microcirculation during free flap surgery: A randomised clinical trial.

BACKGROUND: Macro, and microcirculatory effects of crystalloids and colloids are difficult to compare, because interventions to achieve haemodynamic stability seldom follow similar criteria. OBJECTIVES: Our aim was to compare the effects of crystalloids and colloids on the microcirculation during free flap surgery when management was guided by detailed haemodynamic assessment. DESIGN: A randomised, controlled clinical trial. SETTINGS: The investigation was performed at the University of Szeged, Hungary. PATIENTS: Patients undergoing maxillofacial tumour resection and free flap reconstruction were randomised into groups treated with either intra-operative crystalloid (Ringerfundin, n = 15) or colloid (6% hydroxyethyl starch, HES, n = 15) solutions. INTERVENTIONS: Macrohaemodynamics were monitored by a noncalibrated device (PulsioFlex-PULSION). Central venous oxygen saturation, venous-to-arterial PCO2-gap, lactate levels and urine output were measured hourly. Maintenance fluid was Ringerfundin (1 ml kg h), and a multimodal, individualised, approach-based algorithm was applied to guide haemodynamic support. Hypovolaemia was treated with Ringerfundin or HES fluid boluses, respectively. The microcirculatory effects were assessed by laser-Doppler flowmetry (PeriFlux 5000 LDPM), with the probe placed on the flap and on a control area. Measurements were performed after the flap was prepared, then 1 and 12 h later. MAIN OUTCOME MEASURES: The primary end-point was microcirculatory perfusion as determined by laser-Doppler flowmetry. RESULTS: There was no difference between the groups regarding patient characteristics. Both groups remained haemodynamically stable throughout due to the use of approximately a 1.5 times higher total fluid volume in the Ringerfundin group than in the HES group: mean ±â€ŠSD: 2581 ±â€Š986 and 1803 ±â€Š497) ml, respectively, (P = 0.011). There was no significant difference in the microcirculatory blood flow between the groups. CONCLUSION: Our results showed that when fluid management was guided by detailed haemodynamic assessment, more crystalloid than colloid was needed to maintain haemodynamic stability, but there was no difference between the effects of crystalloids and colloids on the microcirculation. TRIAL REGISTRATION: ClinicalTrials.gov NCT03288051.

Delta Procalcitonin Is a Better Indicator of Infection Than Absolute Procalcitonin Values in Critically Ill Patients: A Prospective Observational Study.

Purpose. To investigate whether absolute value of procalcitonin (PCT) or the change (delta-PCT) is better indicator of infection in intensive care patients. Materials and Methods. Post hoc analysis of a prospective observational study. Patients with suspected new-onset infection were included in whom PCT, C-reactive protein (CRP), temperature, and leukocyte (WBC) values were measured on inclusion (t 0) and data were also available from the previous day (t -1). Based on clinical and microbiological data, patients were grouped post hoc into infection- (I-) and noninfection- (NI-) groups. Results. Of the 114 patients, 85 (75%) had proven infection. PCT levels were similar at t -1: I-group (median [interquartile range]): 1.04 [0.40-3.57] versus NI-group: 0.53 [0.16-1.68], p = 0.444. By t 0 PCT levels were significantly higher in the I-group: 4.62 [1.91-12.62] versus 1.12 [0.30-1.66], p = 0.018. The area under the curve to predict infection for absolute values of PCT was 0.64 [95% CI = 0.52-0.76], p = 0.022; for percentage change: 0.77 [0.66-0.87], p < 0.001; and for delta-PCT: 0.85 [0.78-0.92], p < 0.001. The optimal cut-off value for delta-PCT to indicate infection was 0.76 ng/mL (sensitivity 80 [70-88]%, specificity 86 [68-96]%). Neither absolute values nor changes in CRP, temperature, or WBC could predict infection. Conclusions. Our results suggest that delta-PCT values are superior to absolute values in indicating infection in intensive care patients. This trial is registered with ClinicalTrials.gov identifier: NCT02311816.

Early procalcitonin kinetics and appropriateness of empirical antimicrobial therapy in critically ill patients: A prospective observational study.

PURPOSE: The purpose was to investigate the value of procalcitonin (PCT) kinetics in predicting the appropriateness of empirical antimicrobial treatment in critically ill patients. MATERIALS AND METHODS: This prospective observational study recruited patients in whom empirical antimicrobial therapy was started for suspected infection. Biochemical and physiological parameters were measured before initiating antimicrobials (t0), 8 hourly (t8, t16, t24), and then daily (day2-6). Patients were grouped post hoc into appropriate (A) and inappropriate (IA) groups. RESULTS: Of 209 patients, infection was confirmed in 67%. Procalcitonin kinetics were different between the IA (n = 33) and A groups (n = 108). In the IA group, PCT levels (median [interquartile range]) increased: t0= 2.8 (1.2-7.4), t16= 8.6 (4.8-22.1), t24= 14.5 (4.9-36.1), P< .05. In the A group, PCT peaked at t16 and started to decrease by t24: t0= 4.2 (1.9-12.8), t16= 6.99 (3.4-29.1), t24= 5.2 (2.0-16.7), P< .05. Receiver operating characteristic analysis revealed that a PCT elevation greater than or equal to 69% from t0 to t16 had an area under the curve for predicting inappropriate antimicrobial treatment of 0.73 (95% confidence interval, 0.63-0.83), P< .001; from t0 to t24, a greater than or equal to 74% increase had an area under the curve of 0.86 (0.77-0.94), P< .001. Hospital mortality was 37% in the A group and 61% in the IA group (P= .017). CONCLUSIONS: Early response of PCT in the first 24 hours of commencing empirical antimicrobials in critically ill patients may help the clinician to evaluate the appropriateness of therapy.

Continuous central venous oxygen saturation assisted intraoperative hemodynamic management during major abdominal surgery: a randomized, controlled trial.

BACKGROUND: Major abdominal surgery is associated with significant risk of morbidity and mortality in the perioperative period. Optimising intraoperative fluid administration may result in improved outcomes. Our aim was to compare the effects of central venous pressure (CVP), and central venous oxygen saturation (ScvO2)-assisted fluid therapy on postoperative complications in patients undergoing high risk surgery. METHODS: Patients undergoing elective major abdominal surgery were randomised into control and ScvO2 groups. The target level of mean arterial pressure (MAP) was ≥ 60 mmHg in both groups. In cases of MAP < 60 mmHg patients received either a fluid or vasopressor bolus according to the CVP < 8 mmHg in the control group. In the ScvO2 group, in addition to the MAP, an ScvO2 of <75% or a >3% decrease indicated need for intervention, regardless of the actual MAP. Data are presented as mean ± standard deviation or median (interquartile range). RESULTS: We observed a lower number of patients with complications in the ScvO2 group compared to the control group, however it did not reach statistical significance (ScvO2 group: 10 vs. CONTROL GROUP: 19; p = 0.07). Patients in the ScvO2 group (n = 38) received more colloids compared to the control group (n = 41) [279(161) vs. 107(250) ml/h; p < 0.001]. Both groups received similar amounts of crystalloid (1126 ± 471 vs. 1049 ± 431 ml/h; p = 0.46) and norepinephrine [37(107) vs. 18(73) mcg/h; p = 0.84]. Despite similar blood loss in both groups, the ScvO2 group received more blood transfusions (63% vs. 37%; p = 0.018). More patients in the control group had a postoperative PaO2/FiO2 < 200 mmHg (23 vs. 10, p < 0.01). Twenty eight day survival was significantly higher in the ScvO2 group (37/38 vs. 33/41 p = 0.018). CONCLUSION: ScvO2-assisted intraoperative haemodynamic support provided some benefits, including significantly better postoperative oxygenation and 28 day survival rate, compared to CVP-assisted therapy without a significant effect on postoperative complications during major abdominal surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT02337010.

Effects of IgM-enriched immunoglobulin therapy in septic-shock-induced multiple organ failure: pilot study.

Mortality due to septic-shock-induced respiratory failure remains high. A recent meta-analysis suggested that IgM-enriched immunoglobulin treatment may be beneficial in these patients. In this prospective randomised controlled pilot study we investigated the effects of IgM-enriched immunoglobulin treatment in patients with early septic shock accompanied by severe respiratory failure. 33 patients were randomly allocated to receive 5 ml/kg (predicted body weight) IgM-enriched immunoglobulin (16 patients) or placebo (17 patients), respectively, via 8 h IV-infusion for three consecutive days. Daily Multiple Organ Dysfunction Scores (MODS) were calculated. Serum C-reactive protein (CRP) and procalcitonin (PCT) levels were monitored daily. For statistical analysis two-way ANOVA was used. Daily MODS showed ongoing multiple system organ failure without significant resolution during the 8 days. Median length of ICU stay, mechanical ventilation, vasopressor support during the ICU stay and 28-day mortality were nearly identical in the two groups. Serum PCT levels showed no significant difference between the two groups, however, CRP levels were significantly lower in the IgM-enriched immunoglobulin group on days 4, 5 and 6, respectively. In this study the use of IgM-enriched immunoglobulin preparation failed to produce any improvement in the organ dysfunction as compared to standard sepsis therapy.

Can we Improve Outcome in High Risk Surgery?

Despite the small number of high-risk surgical patients in comparison to all surgical patients, they account for the largest proportion of overall perioperative mortality. Goal directed hemodynamic support may result in a lower incidence of complications and reduced length of hospital stay in these patients. Beyond the standard monitoring of circulation, such as blood pressure and heart rate, further parameters and procedures such as pulse pressure/stroke volume variation-, stroke volume/cardiac index-, and central venous oxygen saturation-guided resuscitation may improve the outcome of high-risk surgical patients. The aim of this review is to focus on the results of animal and clinical studies investigating the usefulness of these indices in the context of goal-directed perioperative support.

Hemodynamic and respiratory changes during lung recruitment and descending optimal positive end-expiratory pressure titration in patients with acute respiratory distress syndrome.

OBJECTIVES: To investigate respiratory and hemodynamic changes during lung recruitment and descending optimal positive end-expiratory pressure (PEEP) titration. DESIGN: Prospective auto-control clinical trial. SETTING: Adult general intensive care unit in a university hospital. PATIENTS: Eighteen patients with acute respiratory distress syndrome. INTERVENTIONS: Following baseline measurements (T0), PEEP was set at 26 cm H2O and lung recruitment was performed (40/40-maneuver). Then tidal volume was set at 4 mL/kg (T26R) and PEEP was lowered by 2 cm H2O in every 4 mins. Optimal PEEP was defined at 2 cm H2O above the PEEP where Pao2 dropped by > 10%. After setting the optimal PEEP, the 40/40-maneuver was repeated and tidal volume set at 6 mL/kg (T(end)). MEASUREMENTS AND MAIN RESULTS: Arterial blood gas analysis was done every 4 mins and hemodynamic measurements every 8 mins until T(end), then in 30 (T30) and 60 (T60) mins. The Pao2 increased from T0 to T(end) (203 +/- 108 vs. 322 +/- 101 mm Hg, p < .001), but the extravascular lung water (EVLW) did not change significantly. Cardiac index (CI) and the intrathoracic blood volume (ITBV) decreased from T0 to T26R (CI, 3.90 +/- 1.04 vs. 3.62 +/- 0.91 L/min/m2, p < .05; ITBVI, 832 +/- 205 vs. 795 +/- 188 m/m2, p < .05). There was a positive correlation between CI and ITBVI (r = .699, p < .01), a negative correlation between CI and central venous pressure (r = -.294, p < .01), and no correlation between CI and mean arterial pressure (MAP). CONCLUSIONS: Following lung recruitment and descending optimal PEEP titration, the Pao2 improves significantly, without any change in the EVLW up to 1 hr. This suggests a decrease in atelectasis as a result of recruitment rather than a reduction of EVLW. There is a significant change in CI during the maneuver, but neither central venous pressure, heart rate, nor MAP can reflect these changes.

Effects of volumetric vs. pressure-guided fluid therapy on postoperative inflammatory response: a prospective, randomized clinical trial.

OBJECTIVE: To compare intrathoracic blood volume (ITBV) guided fluid management and central venous pressure (CVP) guided therapy in ameliorating the progression of early systemic inflammatory response in patients undergoing major surgery. DESIGN: Prospective, randomized clinical trial. PATIENTS: Forty patients undergoing major abdominal surgery were randomized into CVP and ITBV groups. INTERVENTIONS: In the CVP group the target CVP was 8-12 mmHg while in the ITBV group the goal was to keep the ITBV between 850 and 950 ml/m2 during the operation. MEASUREMENTS AND RESULTS: Hemodynamic parameters were determined by single arterial thermodilution. Measurements were repeated every 30 min intraoperatively. Serum procalcitonin (PCT) and C-reactive protein (CRP) was monitored preoperatively, on ICU admission, and then daily for 3 days. Serum TNF-alpha levels were measured intraoperatively hourly and then daily for 3 days. There was no significant difference between the two groups regarding hemodynamic parameters at any assessment point. In the overall population changes in the stroke volume index showed a significant correlation with changes in CVP and ITBV. TNF-alpha levels remained in the normal range intraoperatively and during the three postoperative days in both groups. Preoperatively normal PCT and CRP levels increased significantly postoperatively, without significant differences between the groups. CONCLUSIONS: ITBV guided fluid therapy did not alter the magnitude of inflammatory response as monitored by serum PCT, CRP, and TNF-alpha in the early postoperative period.

Fluid resuscitation with colloids of different molecular weight in septic shock.

OBJECTIVE: The aim of this study was to investigate the short-term effect of fluid resuscitation with 4% modified fluid gelatine (GEL) versus 6% hydroxyethyl starch (HES) on haemodynamics and oxygenation in patients with septic shock and acute lung injury (ALI). DESIGN: Prospective randomised clinical trial. SETTING: Twenty-bed intensive care unit in a university hospital. PATIENTS: Thirty hypovolemic patients (intrathoracic blood volume index, ITBVI <850 ml/m(2)) in septic shock with ALI were randomised into HES (mean molecular weight: 200,000 Dalton, degree of substitution 0.6) and GEL (mean molecular weight: 30,000 Dalton) groups (15 patients each). INTERVENTIONS: For fluid resuscitation 250 ml/15 min boluses (max. 1,000 ml) were given until the end point of ITBVI >900 ml/m(2) was reached. Repeated haemodynamic measurements were done at baseline (t(b)), at the end point (t(ep)) then at 30 min and 60 min after the end point was reached (t(30), t(60)). Cardiac output, stroke volume, extravascular lung water (EVLW), and oxygen delivery was determined at each assessment point. For statistical analysis two-way ANOVA was used. MEASUREMENTS AND RESULTS: ITBVI, cardiac index, and oxygen delivery index increased significantly at t(ep) and remained elevated for t(30) and t(60), but there was no significant difference between the two groups. The increase in the ITBVI by 100 ml of infusion was similar in both groups (HES: 26+/-19 ml/m(2) vs GEL: 30+/-19 ml/m(2)). EVLW, remained unchanged, and there was no significant difference between the groups (HES, t(b): 8+/-6, t(60): 8+/-6; GEL, t(b): 8+/-3, t(60): 8+/-3 ml/kg). The PaO(2)/FiO(2) did not change significantly over time or between groups (HES, t(b): 207+/-114, t(60): 189+/-78; GEL, t(b): 182+/-85, t(60): 182+/-85 mmHg). CONCLUSION: The results of this study indicate that both HES and GEL infusions caused similar short-term change in ITBVI in septic shock, without increasing EVLW or worsening oxygenation.