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.

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.

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.

Hyperbaric oxygen therapy with short duration intratympanic steroid therapy for sudden hearing loss.

CONCLUSION: The excellent tolerability of intratympanic (IT) steroid offers the possibility to use a high dose, which would appear to be more effective than intravenous (IV) steroid treatment, when both are associated with hyperbaric oxygen (HBO) therapy. OBJECTIVE: The purpose of the study was to assess for the first time the efficacy of the association of IT steroid and HBO therapy in patients presenting idiopathic sudden sensorineural hearing loss (ISSNHL), comparing this protocol with another consisting of IV steroid administration and HBO therapy. METHODS: A total of 48 patients presenting ISSNHL were recruited. Patients were divided into two categories: the severe ISSNHL group with a pure-tone average (PTA) between 70 and 90 dB, and the profound ISSNHL group with a PTA >90 dB. The first protocol consisted of 10 days of HBO therapy together with IV methylprednisolone 1 mg/kg body weight for 7 days; the second protocol consisted of HBO therapy for 10 days, associated with an IT injection of prednisolone at a dose of 62.5 mg/ml, once a day for 3 consecutive days, performed 2 h before the HBO therapy. RESULTS: The overall success rate was superior in the group submitted to IT steroid and HBO therapy. Nevertheless, these clinical results were not statistically significant.

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.

Short-term effects of terlipressin bolus infusion on sublingual microcirculatory blood flow during septic shock.

PURPOSE: Terlipressin bolus infusion may contribute to overshooting increases in systemic vascular resistance with concomitant reductions in systemic blood flow and oxygen delivery. Whether these effects negatively impact on microcirculatory perfusion is still not known. The objective of the present study was, therefore, to elucidate the effects of a single terlipressin bolus dose of 0.5 mg on microcirculatory perfusion in patients with catecholamine-dependent septic shock. METHODS: This prospective clinical cohort study was performed in a multidisciplinary intensive care unit at a university hospital. We enrolled 20 patients suffering from catecholamine-dependent septic shock. After restoring normovolaemia, norepinephrine (NE) was titrated to maintain mean arterial pressure (MAP) between 65 and 75 mmHg. Thereafter, all patients received a bolus infusion of 0.5 mg terlipressin, and NE was adjusted to maintain MAP between the threshold values. Sublingual microcirculatory blood flow of small vessels was assessed by sidestream dark-field imaging. All measurements, including data from right heart catheterization and NE requirements, were obtained at baseline and 6 h after terlipressin administration. RESULTS: Terlipressin stabilized haemodynamics and, at the same time, decreased NE requirements (0.42 ± 0.67 vs. 0.74 ± 0.73 µg/kg per minute, p<0.05). Whereas the pH and arterial lactate concentrations remained unchanged, microcirculatory flow index of small vessels had increased at the end of the 6-h study period (2.6 ± 0.6 vs. 2.0 ± 0.5 units, p<0.05). CONCLUSION: In fluid-resuscitated patients with septic shock (with a MAP between 65 and 75 mmHg), a bolus infusion of 0.5 mg terlipressin was effective in reducing NE requirements without worsening microcirculatory blood flow. Randomized clinical trials are now warranted to verify these preliminary results.

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.

Rescue treatment for noninvasive ventilation failure due to interface intolerance with remifentanil analgosedation: a pilot study.

PURPOSE: To assess the feasibility of remifentanil-based sedation in hypoxemic acute respiratory failure (HARF) patients refusing to continue noninvasive ventilation (NPPV) for intolerance to two different interfaces-helmet and total face mask. DESIGN AND SETTING: Prospective uncontrolled clinical investigation in a 14-bed ICU of an university hospital in Italy. PATIENTS: Thirty-six patients with persistent severe HARF who complained of discomfort and asked for interruption of NPPV session. INTERVENTION: Patients started sedation with remifentanil (0.025 µg kg(-1) min(-1)) and the infusion rate was increased by 0.01 µg kg(-1) min(-1) every minute to a maximum of 0.12 µg kg(-1) min(-1) to obtain patient comfort. MEASUREMENTS AND RESULTS: Twenty-two out of 36 patients (61%) with median (IQR) SAPS II score of 32 (30, 38) continued the NPPV treatment after the introduction of remifentanil infusion. In this success group, median (IQR) respiratory rate decreased from 34 (31, 37) to 24 (20, 26) min(-1) (p < 0.0001) and PaO(2)/FiO(2) ratio increased from 156 (144, 176) to 270 (210, 300) mmHg (p < 0.0001) after 1 h of NPPV with remifentanil-analgosedation either with helmet or total face mask. Fourteen patients failed to continue the noninvasive treatment and were intubated after a mean of 2.5 ± 2.3 h; they showed a respiratory rate decrease from 35 (30, 38) to 27 (25, 35) min(-1) (p = 0.02) and an inability to increase the PaO(2)/FiO(2) ratio above 180 mmHg. The ICU mortality in the failure group patients was 50 versus 14% in the NPPV success group (p < 0.05). The mean remifentanil dose administered was 0.07 ± 0.03 µg kg(-1) min(-1). CONCLUSION: This clinical study suggests that a remifentanil-based sedation protocol can decrease the rate of failure in patients with intolerance to NPPV.

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.

Terlipressin: a promising vasoactive agent in hemodynamic support of septic shock.

BACKGROUND: At present, terlipressin is predominantly used for the management of bleeding gastric and esophageal varices, as well as hepato-renal syndrome secondary to liver cirrhosis. Owing to its high and relatively selective affinity to vascular V1 receptors, terlipressin is also increasingly used as an adjunct vasopressor agent in the management of vasodilatory hyperdynamic septic shock. OBJECTIVE: This review article aims to summarize the available knowledge related to hemodynamic support with terlipressin in septic shock. METHODS: For literature search, PubMed and specific keywords from the MeSH Database were used. RESULTS/CONCLUSIONS: Terlipressin represents an effective pressor agent in patients with catecholamine-unresponsive septic shock. However, caution should be exercised, as terlipressin may contribute dose-dependently to vasoconstriction and a reflectory decrease in cardiac output. Additional studies are needed to clarify: i) the optimal time of therapy institution; ii) the efficacy and the dosages of continuous infusion versus bolus administration; and iii) the safety and efficacy of this compound in comparison with other nonspecific vasopressinergic drugs, such as arginine vasopressin. Whether or not terlipressin may improve the outcome of septic shock patients compared with standard therapy with catecholamines remains to be determined.

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.

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 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.

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.

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.