Microvascular effects of heart rate control with esmolol in patients with septic shock: a pilot study.

OBJECTIVE: ß-blocker therapy may control heart rate and attenuate the deleterious effects of ß-stimulating catecholamines in septic shock. However, their negative chronotropy and inotropy may potentially lead to an inappropriately low cardiac output, with a subsequent compromise of microvascular blood flow. The purpose of the present pilot study was to investigate the effects of reducing heart rate to less than 95 beats per minute in patients with septic shock using the ß-1 adrenoceptor blocker, esmolol, with specific focus on systemic hemodynamics and the microcirculation. DESIGN: Prospective, observational clinical study. SETTING: Multidisciplinary ICU at a university hospital. MEASUREMENTS AND MAIN RESULTS: After 24 hours of initial hemodynamic optimization, 25 septic shock patients with a heart rate greater than or equal to 95 beats per minute and requiring norepinephrine to maintain mean arterial pressure greater than or equal to 65 mm Hg received a titrated esmolol infusion to maintain heart rate less than 95 beats per minute. Sublingual microcirculatory blood flow was assessed by sidestream dark-field imaging. All measurements, including data from right heart catheterization and norepinephrine requirements, were obtained at baseline and 24 hours after esmolol administration. Heart rates targeted between 80 and 94 beats per minute were achieved in all patients. Whereas cardiac index decreased (4.0 [3.5; 5.3] vs 3.1 [2.6; 3.9] L/min/m; p<0.001), stroke volume remained unchanged (34 [37; 47] vs 40 [31; 46] mL/beat/m; p=0.32). Microcirculatory blood flow in small vessels increased (2.8 [2.6; 3.0] vs 3.0 [3.0; 3.0]; p=0.002), while the heterogeneity index decreased (median 0.06 [interquartile range 0; 0.21] vs 0 [0; 0]; p=0.002). PaO2 and pH increased while PaCO2 decreased (all p<0.05). Of note, norepinephrine requirements were significantly reduced by selective ß-1 blocker therapy (0.53 [0.29; 0.96] vs 0.41 [0.22; 0.79] µg/kg/min; p=0.03). CONCLUSIONS: This pilot study demonstrated that heart rate control by a titrated esmolol infusion in septic shock patients was associated with maintenance of stroke volume, preserved microvascular blood flow, and a reduction in norepinephrine requirements.

Risk factors for acute kidney injury in critically ill patients receiving high intravenous doses of colistin methanesulfonate and/or other nephrotoxic antibiotics: a retrospective cohort study.

INTRODUCTION: Use of colistin methanesulfonate (CMS) was abandoned in the 1970s because of excessive nephrotoxicity, but it has been reintroduced as a last-resort treatment for extensively drug-resistant infections caused by gram-negative bacteria (Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumonia). We conducted a retrospective cohort study to evaluate risk factors for new-onset acute kidney injury (AKI) in critically ill patients receiving high intravenous doses of colistin methanesulfonate and/or other nephrotoxic antibiotics. METHODS: The cohort consisted of 279 adults admitted to two general ICUs in teaching hospitals between 1 April 2009 and 30 June 2011 with 1) no evidence on admission of acute or chronic kidney disease; and 2) treatment for more than seven days with CMS and/or other nephrotoxic antimicrobials (NAs, that is, aminoglycosides, glycopeptides). Logistic regression analysis was used to identify risk factors associated with this outcome. RESULTS: The 279 cases that met the inclusion criteria included 147 patients treated with CMS, alone (n = 90) or with NAs (n = 57), and 132 treated with NAs alone. The 111 (40%) who developed AKI were significantly older and had significantly higher Simplified Acute Physiology Score II (SAPS II) scores than those who did not develop AKI, but rates of hypertension, diabetes mellitus and congestive heart failure were similar in the two groups. The final logistic regression model showed that in the 147 patients who received CMS alone or with NAs, onset of AKI during the ICU stay was associated with septic shock and with SAPS II scores ≥43. Similar results were obtained in the 222 patients treated with CMS alone or NAs alone. CONCLUSIONS: In severely ill ICU patients without pre-existing renal disease who receive CMS high-dose for more than seven days, CMS therapy does not appear to be a risk factor for this outcome. Instead, the development of AKI was strongly correlated with the presence of septic shock and with the severity of the patients as reflected by the SAPS II score.

Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial.

IMPORTANCE: ß-Blocker therapy may control heart rate and attenuate the deleterious effects of ß-adrenergic receptor stimulation in septic shock. However, ß-Blockers are not traditionally used for this condition and may worsen cardiovascular decompensation related through negative inotropic and hypotensive effects. OBJECTIVE: To investigate the effect of the short-acting ß-blocker esmolol in patients with severe septic shock. DESIGN, SETTING, AND PATIENTS: Open-label, randomized phase 2 study, conducted in a university hospital intensive care unit (ICU) between November 2010 and July 2012, involving patients in septic shock with a heart rate of 95/min or higher requiring high-dose norepinephrine to maintain a mean arterial pressure of 65 mm Hg or higher. INTERVENTIONS: We randomly assigned 77 patients to receive a continuous infusion of esmolol titrated to maintain heart rate between 80/min and 94/min for their ICU stay and 77 patients to standard treatment. MAIN OUTCOMES AND MEASURES: Our primary outcome was a reduction in heart rate below the predefined threshold of 95/min and to maintain heart rate between 80/min and 94/min by esmolol treatment over a 96-hour period. Secondary outcomes included hemodynamic and organ function measures; norepinephrine dosages at 24, 48, 72, and 96 hours; and adverse events and mortality occurring within 28 days after randomization. RESULTS: Targeted heart rates were achieved in all patients in the esmolol group compared with those in the control group. The median AUC for heart rate during the first 96 hours was -28/min (IQR, -37 to -21) for the esmolol group vs -6/min (95% CI, -14 to 0) for the control group with a mean reduction of 18/min (P < .001). For stroke volume index, the median AUC for esmolol was 4 mL/m2 (IQR, -1 to 10) vs 1 mL/m2 for the control group (IQR, -3 to 5; P = .02), whereas the left ventricular stroke work index for esmolol was 3 mL/m2 (IQR, 0 to 8) vs 1 mL/m2 for the control group (IQR, -2 to 5; P = .03). For arterial lactatemia, median AUC for esmolol was -0.1 mmol/L (IQR, -0.6 to 0.2) vs 0.1 mmol/L for the control group (IQR, -0.3 for 0.6; P = .007); for norepinephrine, -0.11 µg/kg/min (IQR, -0.46 to 0.02) for the esmolol group vs -0.01 µg/kg/min (IQR, -0.2 to 0.44) for the control group (P = .003). Fluid requirements were reduced in the esmolol group: median AUC was 3975 mL/24 h (IQR, 3663 to 4200) vs 4425 mL/24 h(IQR, 4038 to 4775) for the control group (P < .001). We found no clinically relevant differences between groups in other cardiopulmonary variables nor in rescue therapy requirements. Twenty-eight day mortality was 49.4% in the esmolol group vs 80.5% in the control group (adjusted hazard ratio, 0.39; 95% CI, 0.26 to 0.59; P < .001). CONCLUSIONS AND RELEVANCE: For patients in septic shock, open-label use of esmolol vs standard care was associated with reductions in heart rates to achieve target levels, without increased adverse events. The observed improvement in mortality and other secondary clinical outcomes warrants further investigation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01231698.

Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock.

INTRODUCTION: The present study was designed to determine the effects of continuously infused norepinephrine (NE) plus (1) terlipressin (TP) or (2) arginine vasopressin (AVP) or (3) placebo on sublingual microcirculation in septic shock patients. The primary study end point was a difference of ≥ 20% in the microvascular flow index of small vessels among groups. METHODS: The design of the study was a prospective, randomized, double-blind clinical trial. NE was titrated to maintain mean arterial pressure (MAP) between 65 and 75 mmHg after establishment of normovolemia in 60 septic shock patients. Thereafter patients (n = 20 per group) were randomized to receive continuous infusions of either TP (1 µg/kg/hour), AVP (0.04 U/minute) or placebo (isotonic saline). In all groups, open-label NE was adjusted to maintain MAP within threshold values if needed. The sublingual microcirculatory blood flow of small vessels was assessed by sidestream dark-field imaging. All measurements, including data from right heart catheterization and norepinephrine requirements, were obtained at baseline and 6 hours after randomization. RESULTS: TP and AVP decreased NE requirements at the end of the 6-hour study period. The data are medians (25th and 75th interquartile ranges (IQRs)): 0.57 µg/kg/minute (0.29 to 1.04) vs. 0.16 µg/kg/minute (0.03 to 0.37) for TP and 0.40 µg/kg/minute (0.20 to 1.05) vs. 0.23 µg/kg/minute (0.03 to 0.77) for AVP, with statistical significance of P < 0.05 vs. baseline and vs. placebo. There were no differences in sublingual microcirculatory variables, systemic hemodynamics, oxygen transport and acid-base homeostasis among the three study groups during the entire observation period. The proportions of perfused vessels increased in relation to baseline within all study groups, and there were no significant differences between groups. The specific data were as follows (median (IQR)): 9.7% (2.6 to 19.8) for TP, 8.9% (0.0 to 17.8) for AVP, and 6.9% (3.5 to 10.1) for placebo (P < 0.05 vs. baseline for each comparison), as well as perfused vessel density 18.6% (8.6 to 36.9) for TP, 20.2% (-3.0 to 37.2) for AVP, and 11.4% (-3.0 to 19.4) for placebo (P < 0.05 vs. baseline for each comparison). CONCLUSIONS: The present study suggests that to achieve a MAP of 65 to 75 mmHg in septic patients treated with NE, the addition of continuously infused low-dose TP or AVP does not affect sublingual microcirculatory blood flow. In addition, our results suggest that microcirculatory flow abnormalities are mainly related to other factors (for example, volume status, timing, hemodynamics and progression of the disease) rather than to the vasopressor per se. TRIAL REGISTRATION: ClinicalTrial.gov NCT00995839.

Learning curves of the Airtraq and the Macintosh laryngoscopes for tracheal intubation by novice laryngoscopists: a clinical study.

BACKGROUND: The curved laryngoscope blade described by Macintosh in 1943 remains the most widely used device to facilitate tracheal intubation. The Airtraq laryngoscope is a new, single-use device for tracheal intubation. Several studies compared the use of Airtraq and Macintosh laryngoscopes in simulated intubation scenarios on manikins. We evaluated learning and performance of tracheal intubation by novice laryngoscopists using the Airtraq or Macintosh laryngoscopes in a randomized controlled clinical trial. METHODS: One hundred eight consecutive patients scheduled for surgical procedures requiring tracheal intubation were enrolled. Patients were randomly allocated to undergo tracheal intubation using a Macintosh (n = 54) or an Airtraq (n = 54) laryngoscope. Tracheal intubation was performed by first-year residents who had no prior experience with the use of either laryngoscope. Primary end points were duration of tracheal intubation and intubation difficulty scale score for both devices. RESULTS: Eighteen residents participated in the protocol; 9 were allocated to each study group. Each participant performed at least 6 tracheal intubations with the same device. We observed a more rapid skill acquisition with the Airtraq than with the Macintosh laryngoscope, as demonstrated by the shorter duration of intubation with the Airtraq laryngoscope. Data analysis with the Student t test revealed a significant difference between the groups (P < 0.001). CONCLUSION: The Airtraq laryngoscope facilitates a more rapid learning curve compared with the Macintosh laryngoscope when used in a clinical setting by novice laryngoscopists. The Airtraq laryngoscope was judged easier to use by novice users.

Levosimendan for resuscitating the microcirculation in patients with septic shock: a randomized controlled study.

INTRODUCTION: The purpose of the present study was to investigate microcirculatory blood flow in patients with septic shock treated with levosimendan as compared to an active comparator drug (i.e. dobutamine). The primary end point was a difference of ≥ 20% in the microvascular flow index of small vessels (MFIs) among groups. METHODS: The study was designed as a prospective, randomized, double-blind clinical trial and performed in a multidisciplinary intensive care unit. After achieving normovolemia and a mean arterial pressure of at least 65 mmHg, 40 septic shock patients were randomized to receive either levosimendan 0.2 µg·kg(-1)·min(-1) (n = 20) or an active comparator (dobutamine 5 µg·kg(-1)·min(-1); control; n = 20) for 24 hours. Sublingual microcirculatory blood flow of small and medium vessels was assessed by sidestream dark-field imaging. Microcirculatory variables and data from right heart catheterization were obtained at baseline and 24 hours after randomization. Baseline and demographic data were compared by means of Mann-Whitney rank sum test or chi-square test, as appropriate. Microvascular and hemodynamic variables were analyzed using the Mann-Whitney rank sum test. RESULTS: Microcirculatory flow indices of small and medium vessels increased over time and were significantly higher in the levosimendan group as compared to the control group (24 hrs: MFIm 3.0 (3.0; 3.0) vs. 2.9 (2.8; 3.0); P = .02; MFIs 2.9 (2.9; 3.0) vs. 2.7 (2.3; 2.8); P < .001). The relative increase of perfused vessel density vs. baseline was significantly higher in the levosimendan group than in the control group (dMFIm 10 (3; 23)% vs. 0 (-1; 9)%; P = .007; dMFIs 47 (26; 83)% vs. 10 (-3; 27); P < .001). In addition, the heterogeneity index decreased only in the levosimendan group (dHI -93 (-100; -84)% vs. 0 (-78; 57)%; P < .001). There was no statistically significant correlation between systemic and microcirculatory flow variables within each group (each P > .05). CONCLUSIONS: Compared to a standard dose of 5 µg·kg(-1)·min(-1) of dobutamine, levosimendan at 0.2 µg·kg(-1)·min(-1) improved sublingual microcirculatory blood flow in patients with septic shock, as reflected by changes in microcirculatory flow indices of small and medium vessels. TRIAL REGISTRATION: NCT00800306.

Post-operative nausea and vomiting (PONV) after thyroid surgery: a prospective, randomized study comparing totally intravenous versus inhalational anesthetics.

The incidence of postoperative nausea and vomiting (PONV) after thyroidectomy and the association of Propofol versus Sevoflurane use for anesthesia maintenance were investigated during a randomized, prospective study. One hundred and ninety-eight patients underwent thyroidectomy receiving either Sevoflurane (0.5-1.3% end-tidal) or Propofol (50-200 mg/kg/min) for anesthesia maintenance. All patients received Propofol for induction of anesthesia, Succinylcholine or Vecuronium, Nitrous Oxide, and Fentanyl. Prophylactic antiemetics were not administered. The combined incidence of PONV was 54.4 per cent over the 24-hour postoperative evaluation period. PONV was more common in patients receiving Sevoflurane than Propofol for maintenance of anesthesia (64.6% vs 43.8%). In women (n = 117), the incidence of PONV resulted higher when receiving inhalational Sevoflurane than Propofol for maintenance (70.6% vs 42.4%). However, in men (n = 81), there was no significant difference in PONV between anesthetic regimens (47.4% with Sevoflurane vs 49.6% with Propofol). Patients undergoing thyroid surgery are at high risk for the development of PONV. Propofol for maintenance of anesthesia, although more expensive than Sevoflurane, may reduce the rate of PONV.

Continuous terlipressin versus vasopressin infusion in septic shock (TERLIVAP): a randomized, controlled pilot study.

INTRODUCTION: Recent clinical data suggest that early administration of vasopressin analogues may be advantageous compared to a last resort therapy. However, it is still unknown whether vasopressin and terlipressin are equally effective for hemodynamic support in septic shock. The aim of the present prospective, randomized, controlled pilot trial study was, therefore, to compare the impact of continuous infusions of either vasopressin or terlipressin, when given as first-line therapy in septic shock patients, on open-label norepinephrine requirements. METHODS: We enrolled septic shock patients (n = 45) with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation. Patients were randomized to receive continuous infusions of either terlipressin (1.3 microg.kg-1.h-1), vasopressin (.03 U.min-1) or norepinephrine (15 microg.min-1; n = 15 per group). In all groups, open-label norepinephrine was added to achieve a mean arterial pressure between 65 and 75 mmHg, if necessary. Data from right heart and thermo-dye dilution catheterization, gastric tonometry, as well as laboratory variables of organ function were obtained at baseline, 12, 24, 36 and 48 hours after randomization. Differences within and between groups were analyzed using a two-way ANOVA for repeated measurements with group and time as factors. Time-independent variables were compared with one-way ANOVA. RESULTS: There were no differences among groups in terms of systemic and regional hemodynamics. Compared with infusion of .03 U of vasopressin or 15 microg.min-1 of norepinephrine, 1.3 microg.kg-1.h-1 of terlipressin allowed a marked reduction in catecholamine requirements (0.8 +/- 1.3 and 1.2 +/- 1.4 vs. 0.2 +/- 0.4 microg.kg-1.min-1 at 48 hours; each P < 0.05) and was associated with less rebound hypotension (P < 0.05). At the end of the 48-hour intervention period, bilirubin concentrations were higher in the vasopressin and norepinephrine groups as compared with the terlipressin group (2.3 +/- 2.8 and 2.8 +/- 2.5 vs. 0.9 +/- 0.3 mg.dL-1; each P < 0.05). A time-dependent decrease in platelet count was only observed in the terlipressin group (P < 0.001 48 hours vs. BL). CONCLUSIONS: The present study provides evidence that continuous infusion of low-dose terlipressin--when given as first-line vasopressor agent in septic shock--is effective in reversing sepsis-induced arterial hypotension and in reducing norepinephrine requirements.

Absorption pharmacokinetics of clonidine nasal drops in children.

BACKGROUND: The alpha2 agonist clonidine has become a popular drug for premedication in children. Effects and pharmacokinetics after oral, rectal, and intravenous administration are well known. The aim of this study was to investigate the absorption pharmacokinetics of clonidine nasal drops in children. METHODS: Thirteen ASA I pediatric patients received after induction of anesthesia 4 mcg x kg(-1) of clonidine by the nasal route. Blood samples were taken during a 12-h period and plasma levels of clonidine were analyzed by liquid chromatography-mass spectrometry. Data were calculated by a computer-aided curve-fitting program. RESULTS: Plasma pharmacokinetics following administration of clonidine nasal drops showed a considerable interindividual variability and absorption was delayed and limited. A total of 95% confidence intervals for maximum plasma concentration and time to achieve maximum plasma concentration were 0.4-0.6 ng x ml(-1) and 1.4-3.0 h, respectively. CONCLUSIONS: Clonidine nasal drops are erratically absorbed from the nasal mucosa and, thus, this mode of drug administration is not recommended for premedication purposes.

Continuous right ventricular end-diastolic volume in comparison with left ventricular end-diastolic area.

BACKGROUND AND OBJECTIVE: Intraoperative management of patients with end-stage liver disease undergoing liver transplantation requires fluid administration to increase cardiac output and oxygen delivery to the tissues. Filling pressures have been widely shown to correlate poorly with changes in cardiac output in the critically ill patient. Continuous right ventricular end-diastolic volume index (cRVEDVI) and left ventricular end-diastolic area index (LVEDAI) monitoring have been increasingly used for preload assessment. The aim of this study was to compare cRVEDVI, LVEDAI, central venous pressure and pulmonary artery occlusion pressure with respect to stroke volume index (SVI) during liver transplantation. METHODS: Measurements were made in 20 patients at four predefined steps during liver transplantation. Univariate and multivariate panel-data fixed effect regression models (across phases of the surgical procedure) were fitted to assess associations between SVI and cRVEDVI, pulmonary artery occlusion pressure, central venous pressure and LVEDAI after adjusting for ejection fraction (categorized as 40). RESULTS: SVI was associated with continuous right ventricular ejection fraction. The model showing the best fit to the data was that including cRVEDVI: even after adjusting for continuous right ventricular ejection fraction and phase, the regression coefficient of cRVEDVI in predicting SVI was statistically significant and indicated an increase in SVI of 0.21 ml m(-2) for each increase of 1 ml m(-2). At the multivariate analysis, an increase in LVEDAI of 1 cm m(-2) led to an increase in SVI of 1.47 ml m(-2) (P = 0.054). CONCLUSION: cRVEDVI and LVEDAI gave a better reflection of preload than filling pressure, even if only cRVEDVI reached statistical significance.

Regional cerebral saturation versus transcranial Doppler during carotid endarterectomy under regional anaesthesia.

BACKGROUND AND OBJECTIVE: The aim of this study was to compare a cerebral oximeter with transcranial Doppler (TCD) as a neurological monitor in patients undergoing carotid endarterectomy under regional anaesthesia. METHODS: Forty patients were enrolled for this prospective study. We recorded every adverse neurological event after arterial clamping and variations in parameters evaluated by the two monitoring systems in order to determine whether there was any correlation between TCD data and those obtained by regional cerebral saturation, the timing of detection of the adverse event in both clinical examination and instrumental data and the presence of any false positives or negatives in any of the two monitoring systems. RESULTS: Shunting was necessary in eight patients, following clinical signs of a neurological deficit during clamping. In these patients, a significant reduction in TCD values and regional cerebral saturation values from baseline was recorded. We observed a drastic reduction in TCD values in four patients during clamping (6 +/- 5 versus 41 +/- 4 cm s) that was not associated with any neurological deficit or reduction in regional cerebral saturation values (51 +/- 4 versus 54 +/- 7%). Instrumental detection of a neurological deficit anticipated the clinical observation of about 5-10 s. CONCLUSION: We observed a greater reliability with the cerebral oximeter than with TCD in our patients.

Continuous right ventricular end diastolic volume and right ventricular ejection fraction during liver transplantation: a multicenter study.

Cardiac preload is traditionally considered to be represented by its filling pressures, but more recently, estimations of end diastolic volume of the left or right ventricle have been shown to better reflect preload. One method of determining volumes is the evaluation of the continuous right ventricular end diastolic volume index (cRVEDVI) on the basis of the cardiac output thermodilution technique. Because preload and myocardial contractility are the main factors determining cardiac output during liver transplantation (LTx), accurate determination of preload is important. Thus, monitoring of cRVEDVI and cRVEF should help with fluid management and with the assessment of the need for inotropic and vasoactive agents. In this multicenter study, we looked for possible relationships between the stroke volume index (SVI) and cRVEDVI, cRVEF, and filling pressures at 4 predefined steps in 244 patients undergoing LTx. Univariate and multivariate autoregression models (across phases of the surgical procedure) were fitted to assess the possible association between SVI and cRVEDVI, pulmonary artery occlusion pressure (PAOP), and central venous pressure (CVP) after adjustment for cRVEF (categorized as < or =30, 31-40, and >40%). SVI was strongly associated with both cRVEDVI and cRVEF. The model showing the best fit to the data was that including cRVEDVI. Even after adjustment for cRVEF, there was a statistically significant (P < 0.05) relationship between SVI and cRVEDVI with a regression coefficient (slope of the regression line) of 0.25; this meant that an increase in cRVEDVI of 1 mL m(-2) resulted in an increase in SVI of 0.25 mL m(-2). The correlations between SVI and CVP and PAOP were less strong. We conclude that cRVEDVI reflected preload better than CVP and PAOP.

Short-term effects of phenylephrine on systemic and regional hemodynamics in patients with septic shock: a crossover pilot study.

Clinical studies evaluating the use of phenylephrine in septic shock are lacking. The present study was designed as a prospective, crossover pilot study to compare the effects of norepinephrine (NE) and phenylephrine on systemic and regional hemodynamics in patients with catecholamine-dependent septic shock. In 15 septic shock patients, NE (0.82 +/- 0.689 microg x kg(-1) x min(-1)) was replaced with phenylephrine (4.39 +/- 5.23 microg x kg(-1) x min(-1)) titrated to maintain MAP between 65 and 75 mmHg. After 8 h of phenylephrine infusion treatment was switched back to NE. Data from right heart catheterization, acid-base balance, thermo-dye dilution catheter, gastric tonometry, and renal function were obtained before, during, and after replacing NE with phenylephrine. Variables of systemic hemodynamics, global oxygen transport, and acid-base balance remained unchanged after replacing NE with phenylephrine except for a significant decrease in heart rate (phenylephrine, 89 +/- 18 vs. NE, 93 +/- 18 bpm; P < 0.05). However, plasma disappearance rate (phenylephrine, 13.5 +/- 7.1 vs. NE, 16.4 +/- 8.7% x min(-1)) and clearance of indocyanine green (phenylephrine, 330 +/- 197 vs. NE, 380 +/- 227 mL x min(-1) x m(-2)), as well as creatinine clearance (phenylephrine, 81.3 +/- 78.4 vs. NE, 94.3 +/- 93.5 mL x min(-1)) were significantly decreased by phenylephrine infusion (each P < 0.05). In addition, phenylephrine increased arterial lactate concentrations as compared with NE infusion (1.7 +/- 1.0 vs. 1.4 +/- 1.1 mM; P < 0.05). After switching back to NE, all variables returned to values obtained before phenylephrine infusion except creatinine clearance and gastric tonometry values. Our results suggest that for the same MAP, phenylephrine causes a more pronounced hepatosplanchnic vasoconstriction as compared with NE.

Continuous and intermittent cardiac output measurement in hyperdynamic conditions: pulmonary artery catheter vs. lithium dilution technique.

OBJECTIVE: This study aimed to assess the level of agreement of both intermittent cardiac output monitoring by the lithium dilution technique (CO(Li)) and continuous cardiac output monitoring (PulseCO(Li)) using the arterial pressure waveform with intermittent thermodilution using a pulmonary artery catheter (CO(PAC)). DESIGN: Prospective, single-center evaluation. SETTING: University Hospital Intensive Care Unit. PATIENTS: Patients (n=23) receiving liver transplantation. INTERVENTION: Pulmonary artery catheters were placed in all patients and CO(PAC) was determined using thermodilution. CO(Li) and PulseCO(Li) measurements were made using the LiDCO system. MEASUREMENTS AND MAIN RESULTS: Data were collected after intensive care unit admission and every 8h until the 48th hour. A total of 151 CO(PAC), CO(Li) and PulseCO(Li) measurements were analysed. Bias and 95% limit of agreement were 0.11lmin(-1) and -1.84 to + 2.05 lmin(-1) for CO(PAC) vs. CO(Li) (r=0.88) resulting in an overall percentage error of 15.6%. Bias and 95% limit of agreement for CO(PAC) vs. PulseCO(Li) were 0.29 lmin(-1) and -1.87 to + 2.46 lmin(-1) (r=0.85) with a percentage error of 16.8%. Subgroup analysis revealed a percentage error of 15.7% for CO(PAC) vs. CO(Li) and 15.1% for CO(PAC) vs. PulseCO(Li) for data pairs less than 8 lmin(-1), and percentage errors of 15.5% and 18.5% respectively for data pairs higher than 8 lmin(-1). CONCLUSION: In patients with hyperdynamic circulation, intermittent and continuous CO values determined using the LiDCO system showed good agreement with those obtained by intermittent pulmonary artery thermodilution.

Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: a randomized, controlled trial.

INTRODUCTION: Previous findings suggest that a delayed administration of phenylephrine replacing norepinephrine in septic shock patients causes a more pronounced hepatosplanchnic vasoconstriction as compared with norepinephrine. Nevertheless, a direct comparison between the two study drugs has not yet been performed. The aim of the present study was, therefore, to investigate the effects of a first-line therapy with either phenylephrine or norepinephrine on systemic and regional hemodynamics in patients with septic shock. METHODS: We performed a prospective, randomized, controlled trial in a multidisciplinary intensive care unit in a university hospital. We enrolled septic shock patients (n = 32) with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation. Patients were randomly allocated to treatment with either norepinephrine or phenylephrine infusion (n = 16 each) titrated to achieve a mean arterial pressure between 65 and 75 mmHg. Data from right heart catheterization, a thermodye dilution catheter, gastric tonometry, acid-base homeostasis, as well as creatinine clearance and cardiac troponin were obtained at baseline and after 12 hours. Differences within and between groups were analyzed using a two-way analysis of variance for repeated measurements with group and time as factors. Time-independent variables were compared with one-way analysis of variance. RESULTS: No differences were found in any of the investigated parameters. CONCLUSIONS: The present study suggests there are no differences in terms of cardiopulmonary performance, global oxygen transport, and regional hemodynamics when phenylephrine was administered instead of norepinephrine in the initial hemodynamic support of septic shock. TRIAL REGISTRATION: ClinicalTrial.gov NCT00639015.

Arterial pulse cardiac output agreement with thermodilution in patients in hyperdynamic conditions.

OBJECTIVE: This study aimed to compare continuous cardiac output (CCO) obtained using the arterial pulse wave (APCO) measurement with a simultaneous measurement of the intermittent cardiac output (ICO) and CCO obtained with a pulmonary artery catheter (PAC) in liver transplant patients. DESIGN: A prospective, single-center evaluation. SETTING: A university hospital intensive care unit. PATIENTS: Eighteen patients after liver transplantation. INTERVENTIONS: Pulmonary artery catheters were placed in all patients, and ICO and CCO were determined using thermodilution. APCO measurements were made with the Vigileo System (Edwards Lifesciences, Irvine, CA). MEASUREMENTS AND MAIN RESULTS: The authors obtained 126 data pairs of ICO and APCO and 864 pairs of CCO and APCO. ICO data were collected after intensive care unit admission and every 8 hours until the 48th postoperative hour. CCO and APCO data were collected every hour from admission until the 48th postoperative hour. Bias and precision were 0.95 +/- 1.41 L/min for ICO versus APCO and 1.29 +/- 1.28 L/min for CCO and APCO. Bias and precision for cardiac output (CO) data pairs less than 8 L/min were 0.32 +/- 1.14 L/min between ICO and APCO and 0.71 +/- 0.98 L/min between CCO and APCO. For CO data pairs higher than 8 L/min, bias and precision were 1.79 +/- 1.54 L/min between ICO and APCO and 2.25 +/- 1.14 L/min between CCO and APCO. CONCLUSIONS: APCO enables the assessment of CO with clinically acceptable bias and precision. At higher CO levels, APCO underestimates PAC measurements and it is not as reliable as thermodilution in hyperdynamic liver transplant patients.

Glibenclamide dose response in patients with septic shock: effects on norepinephrine requirements, cardiopulmonary performance, and global oxygen transport.

Adenosine triphosphate-sensitive potassium channels are important regulators of arterial vascular smooth muscle tone and are implicated in the pathophysiology of catecholamine tachyphylaxis in septic shock. The present study was designed as a prospective, randomized, double-blinded, clinical pilot study to determine whether different doses of glibenclamide have any effects on norepinephrine requirements, cardiopulmonary hemodynamics, and global oxygen transport in patients with septic shock. We enrolled 30 patients with septic shock requiring invasive hemodynamic monitoring and norepinephrine infusion of 0.5 microg.kg-1.min-1 or greater to maintain MAP between 65 and 75 mmHg. In addition to standard therapy, patients were randomized to receive either 10, 20, or 30 mg of enteral glibenclamide. Systemic hemodynamics, global oxygen transport including arterial lactate concentrations, gas exchange, plasma glucose concentrations, and electrolytes were determined at baseline and after 3, 6, and 12 h after administration of the study drug. Glibenclamide decreased plasma glucose concentrations in a dose-dependent manner but failed to reduce norepinephrine requirements. None of the doses had any effects on cardiopulmonary hemodynamics, global oxygen transport, gas exchange, or electrolytes. These data suggest that oral glibenclamide in doses from 10 to 30 mg fails to counteract arterial hypotension and thus to reduce norepinephrine requirements in catecholamine-dependent human septic shock.

Goal-directed intraoperative therapy reduces morbidity and length of hospital stay in high-risk surgical patients.

BACKGROUND: Postoperative organ failures commonly occur after major abdominal surgery, increasing the utilization of resources and costs of care. Tissue hypoxia is a key trigger of organ dysfunction. A therapeutic strategy designed to detect and reverse tissue hypoxia, as diagnosed by an increase of oxygen extraction (O2ER) over a predefined threshold, could decrease the incidence of organ failures. The primary aim of this study was to compare the number of patients with postoperative organ failure and length of hospital stay between those randomized to conventional vs a protocolized strategy designed to maintain O2ER < 27%. METHODS: A prospective, randomized, controlled trial was performed in nine hospitals in Italy. One hundred thirty-five high-risk patients scheduled for major abdominal surgery were randomized in two groups. All patients were managed to achieve standard goals: mean arterial pressure > 80 mm Hg and urinary output > 0.5 mL/kg/h. The patients of the "protocol group" (group A) were also managed to keep O2ER < 27%. MEASUREMENTS AND MAIN RESULTS: In group A, fewer patients had at least one organ failure (n = 8, 11.8%) than in group B (n = 20, 29.8%) [p < 0.05], and the total number of organ failures was lower in group A than in group B (27 failures vs 9 failures, p < 0.001). Length of hospital stay was significantly lower in the protocol group than in the control group (11.3 +/- 3.8 days vs 13.4 +/- 6.1 days, p < 0.05). Hospital mortality was similar in both groups. CONCLUSIONS: Early treatment directed to maintain O2ER at < 27% reduces organ failures and hospital stay of high-risk surgical patients. Clinical trials.gov reference No. NCT00254150.

How to measure and interpret volumetric measures of preload.

PURPOSE OF REVIEW: To update the situation over the past few years on the clinical application of volumetric measures of preload in critically ill patients. RECENT FINDINGS: Cardiac filling pressures monitoring is unreliable for assessing cardiac preload in mechanically ventilated critically ill patients. The transpulmonary dilution indicator technique was shown to better identify preload than pulmonary arterial catheterization. Measuring static preload index as intrathoracic blood volume or global end diastolic volume provides a good preload index, either in experimental or in different clinical settings. SUMMARY: Volumetric measures of preload are good preload indexes. These data are to be interpreted together with the clinical patient's condition, conventional hemodynamic data and the course of illness in critically ill patients. In order to evaluate whether the application of a predefined therapy algorithm based on volumetric monitoring can improve patients' outcome, more studies are needed.

Solute removal during continuous renal replacement therapy in critically ill patients: convection versus diffusion.

INTRODUCTION: The best modality, for continuous renal replacement therapy (CRRT) is currently uncertain and it is poorly understood how transport of different solutes, whether convective or diffusive, changes over time. METHODS: We conducted a prospective cross over study in a cohort of critically ill patients, comparing small (urea and creatinine) and middle (beta2 microglobulin) molecular weight solute clearance, filter lifespan and membrane performance over a period of 72 hours, during 15 continuous veno-venous dialysis (CVVHD) and 15 continuous veno-venous hemofiltration (CVVH)sessions. Both modalities were administered based on a prescription of 35 ml/kg/h and using polyacrylonitrile filters. RESULTS: Median filter lifespan was significantly longer during CVVHD (37 hours, interquartile range (IQR) 19.5 to 72.5) than CVVH (19 hours, IQR 12.5 to 28) (p = 0.03). Median urea time weighted average (TWA) clearances were not significantly different during CVVH (31.6 ml/minute, IQR 23.2 to 38.9) and CVVHD (35.7 ml/minute, IQR 30.1 to 41.5) (p = 0.213). Similar results were found for creatinine: 38.1 ml/minute, IQR 28.5 to 39, and 35.6 ml/minute, IQR 26 to 43 (p = 0.917), respectively. Median beta2m TWA clearance was higher during convective (16.3 ml/minute, IQR 10.9 to 23) than diffusive (6.27 ml/minute, IQR 1.6 to 14.9) therapy; nonetheless this difference did not reach statistical significance (p = 0.055). Median TWA adsorptive clearance of beta2m appeared to have scarce impact on overall solute removal (0.012 ml/minute, IQR -0.09 to 0.1, during hemofiltration versus -0.016 ml/minute, IQR -0.08 to 0.1 during dialysis; p = 0.79). Analysis of clearance modification over time did not show significant modifications of urea, creatinine and beta2m clearance in the first 48 hours during both treatments. In the CVVHD group, the only significant difference was found for beta2m between 72 hours and baseline clearance. CONCLUSION: Polyacrylonitrile filters during continuous hemofiltration and continuous hemodialysis delivered at 35 ml/kg/h are comparable in little and middle size solute removal. CVVHD appears to warrant longer CRRT sessions. The capacity of both modalities for removing such molecules is maintained up to 48 hours.