Javier Belda

Perioperative goal-directed hemodynamic therapy based on radial arterial pulse pressure variation and continuous cardiac index trending reduces postoperative complications after major abdominal surgery: a multi-center, prospective, randomized study.

IntroductionSeveral single-center studies and meta-analyses have shown that perioperative goal-directed therapy may significantly improve outcomes in general surgical patients. We hypothesized that using a treatment algorithm based on pulse pressure variation, cardiac index trending by radial artery pulse contour analysis, and mean arterial pressure in a study group (SG), would result in reduced complications, reduced length of hospital stay and quicker return of bowel movement postoperatively in abdominal surgical patients, when compared to a control group (CG).Methods160 patients undergoing elective major abdominal surgery were randomized to the SG (79 patients) or to the CG (81 patients). In the SG hemodynamic therapy was guided by pulse pressure variation, cardiac index trending and mean arterial pressure. In the CG hemodynamic therapy was performed at the discretion of the treating anesthesiologist. Outcome data were recorded up to 28 days postoperatively.ResultsThe total number of complications was significantly lower in the SG (72 vs. 52 complications, p = 0.038). In particular, infection complications were significantly reduced (SG: 13 vs. CG: 26 complications, p = 0.023). There were no significant differences between the two groups for return of bowel movement (SG: 3 vs. CG: 2 days postoperatively, p = 0.316), duration of post anesthesia care unit stay (SG: 180 vs. CG: 180 minutes, p = 0.516) or length of hospital stay (SG: 11 vs. CG: 10 days, p = 0.929).ConclusionsThis multi-center study demonstrates that hemodynamic goal-directed therapy using pulse pressure variation, cardiac index trending and mean arterial pressure as the key parameters leads to a decrease in postoperative complications in patients undergoing major abdominal surgery.Trial registrationClinicalTrial.gov, NCT01401283.

Virological and immunological features of active cytomegalovirus infection in nonimmunosuppressed patients in a surgical and trauma intensive care unit.

Cytomegalovirus (CMV) reactivation occurs frequently in critically ill patients. The natural course of CMV infection and the interaction between CMV and the adaptive immune system in this setting remain poorly defined. Fifty‐three CMV‐seropositive patients in a surgical and trauma intensive care unit were included in this study. The CMV DNA load in tracheal aspirates (TA) and plasma (PL) was monitored by qPCR. CMV‐specific T‐cell immunity was assessed by intracellular cytokine staining. Plasma TNF‐α levels were determined by ELISA. CMV reactivation occurred in 39.7% of patients (23% had CMV DNA detected only in TA). The analysis of TA allowed an earlier diagnosis in 28% of patients. Clearance of CMV DNAemia preceded that of CMV DNA in TA in some episodes. Peak CMV DNA levels were significantly higher in TA than in PL (P = 0.02). CMV reactivation developed in the presence of CMV‐specific T cells. Termination of CMV reactivation was associated with an expansion of functional CMV‐specific T cells. Plasma levels of TNF‐α did not allow for the prediction of the occurrence of CMV reactivation. CMV‐specific T‐cell immunity is preserved in most critically ill patients experiencing CMV reactivation. Analysis of respiratory specimens is imperative for an optimal monitoring of CMV reactivation in this setting. J. Med. Virol. 82:1384–1391, 2010.

The Predictive Performance of a Pharmacokinetic Model for Manually Adjusted Infusion of Liquid Sevofluorane for Use with the Anesthetic-Conserving Device (AnaConDa) : A Clinical Study

BACKGROUND: The Anesthetic-Conserving Device (AnaConDa) can be used to administer inhaled anesthetics using an intensive care unit (ICU) ventilator. We evaluated the predictive performance of a simple manually adjusted pump infusion scheme, for infusion of liquid sevoflurane to the AnaConDa. METHODS: We studied 50 ICU patients who received sevoflurane via the AnaConDa. They were randomly divided into three groups. A 6-h infusion of liquid anesthetic was adjusted according to the infusion scheme to a target end-tidal sevoflurane concentration of 1% (Group 1%, n = 15) and 1.5% (Group 1.5%, n = 15). The initial rate was adjusted to reach the target concentration in 10 min and then the infusion was reduced to the first hour maintenance rate and readjusted once each hour afterwards. The actual concentrations were measured in the breathing circuit and compared with the target values. In the third group (n = 20) we used the model to increase and decrease the target concentration (±0.3%) for 3 h and evaluated the actual change in concentration achieved. The ability of the infusion scheme to provide the target concentration was quantified by calculating the performance error (PE). Infusion scheme performance was evaluated in terms of accuracy (median absolute PE, MDAPE) and bias (median PE, MDPE). RESULTS: Performance parameters (mean ± sd, %) were for 1%, 1.5%, increase of concentration by 0.3% and decrease of concentration by 0.3% groups, respectively: MDAPE 5.3 ± 5.5, 2.6 ± 4.0, 5.0 ± 5.6, 5.5 ± 5.4; MDPE −5.3 ± 5.5, −2.3 ± 4.1, −0.1 ± 7.1, 0.2 ± 5.4. No significant differences were found between means of all performance parameters when the 1% and 1.5% groups were compared. CONCLUSIONS: There is an excellent 6-h predictive performance of a simplified pharmacokinetic model for manually adjusted infusion of liquid sevoflurane when using the AnaConDa to deliver sevoflurane to ICU patients.

Technical Performance and Reflection Capacity of the Anaesthetic Conserving Device—A Bench Study with Isoflurane and Sevoflurane

ObjectiveThe anaesthetic conserving device (AnaConDa®, Sedana Medical, Sundbyberg, Sweden) facilitates administration of isoflurane or sevoflurane by liquid infusion. An anaesthetic reflector inside the device conserves exhaled anaesthetic and re-supplies it during inspiration. In this bench study, we examined the influence of infusion rates and ventilatory settings on the resulting anaesthetic concentrations on patient (Cpat) and ventilator side of the reflector (Closs) to describe its technical performance.MethodsA Puritan Bennett 840 ICU ventilator (Pleasanton, US), AnaConDa®, and a test lung (3 l-chloroprene-bag) were assembled. Infusion rates (IR, 0.2-50 ml h-), respiratory rates (RR, 5-40 breaths min-1), and tidal volumes (VT, 0.3, 0.5, and 1.0 l) were varied. Cpat was measured via a thin catheter in the middle of the 3 l-bag in steady state (online data storage and averaging over >10 min). Closs was calculated from IR (to yield the volume of vapour per unit of time), and expired minute volume (in which the vapour is diluted) on the assumption that, in the steady state, input by liquid infusion equals output through the reflector.ResultsAt lower concentrations (Cpat< 1 vol%) the ratio Closs/Cpat was constant (RC = 0.096 ±±0.012) for all combinations of IR, RR and VT, both for isoflurane and sevoflurane. The device could efficiently reflect up to 10 ml vapour per breath (e.g. 2 vol% in 0.5 l). When exceeding this capacity, surplus vapour “spilled over” and RC markedly increased indicating decreased performance.ConclusionsThe triple product minute volume times RC times Cpat describes anaesthetic losses through the reflector. It can easily be calculated as long as the 10 ml reflection capacity is not exceeded and thus RC is constant. Increased minute ventilation necessitates increasing the IR to keep Cpat constant. When using large VT and high Cpat “spill over” occurs. This effect offers some protection against an inadvertent overdose.

Programming pressure support ventilation in pediatric patients in ambulatory surgery with a laryngeal mask airway

BACKGROUND:Anesthesia workstations with pressure support ventilation (PSV) are available, but there are few studies published on how to program flow-triggered PSV using a laryngeal mask airway (LMA) under general anesthesia in pediatric patients. METHODS:We studied 60 ASA I and II patients, from 2 mo to 14 yr, scheduled for ambulatory surgery under combined general and regional anesthesia with a LMA. Patients were classified according to their body weight as follows: Group A ≤10 kg, Group B 11–20 kg, and Group C >20 kg. All were ventilated in PSV using the following settings: positive end-expiratory pressure of 4 cm H2O, the minimum flow-trigger without provoking auto-triggering, and the minimum level of pressure support to obtain 10 mL/kg of tidal volume. RESULTS:The flow-trigger most frequently used in our study was 0.4 L/min, ranging from 0.2 to 0.6 L/min. We found no correlation between the flow-trigger setting and the patient’s age, weight, compliance, resistance, or respiratory rate. There was a good correlation between the level of pressure support (Group A = 15 cm H2O, Group B = 10 cm H2O and Group C = 9 cm H2O) and age (P < 0.001), weight (P < 0.001), dynamic compliance (P < 0.001), and airway resistances (P < 0.001). CONCLUSIONS:PSV with a Proseal™ LMA in outpatient pediatric anesthesia can be programmed simply using the common clinical noninvasive variables studied. However, more studies are needed to estimate the level of pressure support that may be required in other clinical situations (respiratory pathology, endotracheal tubes, or other types of surgeries) or with other anesthesia workstations.

Evaluation of cytomegalovirus (CMV)-specific t-cell immunity for the assessment of the risk of active CMV infection in non-immunosuppressed surgical and trauma intensive care unit patients

The current study was designed to assess the predictive value of the evaluation of cytomegalovirus (CMV)‐specific T‐cell immunity early following admission to the intensive care unit for inferring the risk of active CMV infection in non‐immunosuppressed surgical and trauma patients. A total of 31 CMV‐seropositive patients were included. Patients were screened for the presence of CMV DNA in plasma and in tracheal aspirates by real‐time PCR. Enumeration of CMV pp65 and IE‐1‐specific IFN‐γ CD8+ and CD4+ T cells was performed by flow cytometry for intracellular cytokine staining. Virological and immunological monitoring was conducted once or twice a week. Active CMV infection occurred in 17 out of 31 patients. Undetectable levels of pp65 and IE‐1‐specific IFN‐γ CD8+ and CD4+ T‐cell subsets cells were observed in 10 patients who developed active CMV infection and in one who did not (at a median of 2 days following ICU admission). Peak CMV DNA loads in both tracheal aspirates and plasma were substantially higher (P = 0.018 and P = 0.091, respectively) in patients with undetectable IFN‐γ T‐cell responses than in patients with detectable responses. The expansion of both CMV‐specific T‐cell subsets following detection of active CMV infection was demonstrated in 9 out of 14 patients with active CMV infection. In conclusion, the evaluation of CMV pp65 and IE‐1‐specific IFN‐γ‐producing CD8+ and CD4+ T cells early following ICU admission may allow the identification of patients most at risk of either having or developing an episode of active CMV infection, particularly those associated with high‐level virus replication. J Med. Virol. 85:1802–1810, 2013.

Myocardial oxidative stress protection by sevoflurane vs. propofol: a randomised controlled study in patients undergoing off-pump coronary artery bypass graft surgery.

Context Myocardial oxidative stress plays an essential role in the pathogenesis of ischaemia–reperfusion injury associated with coronary artery bypass grafting (CABG). Both propofol and volatile anaesthetics have been shown to reduce reactive oxygen species in experimental and clinical studies. Main objective To compare the influence of sevoflurane and propofol on myocardial oxidative stress markers (F2-isoprostanes and nitrates/nitrites) in coronary sinus blood samples from patients undergoing off-pump CABG. Design and setting Randomised controlled clinical study of patients scheduled for off-pump CABG in a tertiary academic university hospital from June 2007 to August 2009. Forty patients consented to enrolment and were assigned to receive either propofol or sevoflurane. Interventions Upon completion of the proximal anastomosis, a retroplegia cannula was inserted in the coronary sinus to obtain blood samples, according to the study protocol. Main outcome measures Markers of lipoperoxidation (F2-isoprostanes) and nitrosative stress (nitrates/nitrites) were measured in coronary sinus blood samples at three time points: after the end of the proximal anastomosis (T1), after completion of all grafts (T2) and 15 min after revascularisation (T3). Results Of the 40 recruited patients, 38 fully completed the study. In the sevoflurane group (n = 20), concentrations of oxidative stress markers in the coronary sinus remained almost constant and were significantly lower than those in the propofol group (n = 18) at all time points. F2-isoprostanes concentrations were as follows at T1: sevoflurane group 37.2 ± 27.5 pg ml−1 vs. propofol group 170.7 ± 30.9 pg ml−1 [95% confidence interval (CI) 112.16–155.08, P < 0.0001); at T2: sevoflurane group 31.94 ± 24.6 pg ml−1 vs. propofol group 171.6 ± 29.7 pg ml−1 (95% CI 119.78–159.63, P < 0.0001); and at T3: sevoflurane group 23.8 ± 13.0 pg ml−1 vs. propofol group 43.6 ± 31 pg ml−1 (95% CI 2.87–36.63, P = 0.023). Conclusion In patients undergoing off-pump CABG, sevoflurane showed better antioxidative properties than propofol.

Low-flow anesthesia and reduced animal size increase carboxyhemoglobin levels in swine during desflurane and isoflurane breakdown in dried soda lime.

UNLABELLED After institutional approval, we studied the effect of animal size, anesthetic concentration, and fresh gas flow (FGF) rate on inspired carbon monoxide (CO) and carboxyhemoglobin (COHb) during anesthesia in swine, using soda lime previously dried to 1 +/- 0.1% water content. To ascertain the effect of anesthesia, eight adult pigs were anesthetized with either 1 minimum alveolar anesthetic concentration (MAC) desflurane or isoflurane and, to characterize the effect of the FGF rate, it was doubled in four pigs. To determine the effect of animal size, four small and four large pigs received 1 MAC desflurane or isoflurane, and to determine the effect of the anesthetic concentration, a group of four swine was exposed to 0.5 MAC. CO and COHb concentrations were larger with desflurane (5500 +/- 980 ppm and 57.90% +/- 0.50%, respectively) than with isoflurane (800 ppm and 17.8% +/- 2.14%, respectively), especially in the small animals. Increasing the FGF rate significantly reduced peak CO and COHb concentrations resulting from both anesthetics; however, when each anesthetic was reduced to 0.5 MAC, the concentrations obtained were similar. We conclude that CO intoxication is more severe with desflurane than with isoflurane, that small animals are at higher risk for CO poisoning, and that low FGF can increase COHb concentrations. IMPLICATIONS The present study shows that the use of desflurane with desiccated carbon dioxide absorbents in pediatric anesthesia can produce a dangerous carbon dioxide intoxication, especially with low-flow anesthesia.

A Quantile Analysis of Plateau and Driving Pressures: Effects on Mortality in Patients With Acute Respiratory Distress Syndrome Receiving Lung-protective Ventilation.

Objectives: The driving pressure (plateau pressure minus positive end-expiratory pressure) has been suggested as the major determinant for the beneficial effects of lung-protective ventilation. We tested whether driving pressure was superior to the variables that define it in predicting outcome in patients with acute respiratory distress syndrome. Design: A secondary analysis of existing data from previously reported observational studies. Setting: A network of ICUs. Patients: We studied 778 patients with moderate to severe acute respiratory distress syndrome. Interventions: None. Measurements and Main Results: We assessed the risk of hospital death based on quantiles of tidal volume, positive end-expiratory pressure, plateau pressure, and driving pressure evaluated at 24 hours after acute respiratory distress syndrome diagnosis while ventilated with standardized lung-protective ventilation. We derived our model using individual data from 478 acute respiratory distress syndrome patients and assessed its replicability in a separate cohort of 300 acute respiratory distress syndrome patients. Tidal volume and positive end-expiratory pressure had no impact on mortality. We identified a plateau pressure cut-off value of 29 cm H2O, above which an ordinal increment was accompanied by an increment of risk of death. We identified a driving pressure cut-off value of 19 cm H2O where an ordinal increment was accompanied by an increment of risk of death. When we cross tabulated patients with plateau pressure less than 30 and plateau pressure greater than or equal to 30 with those with driving pressure less than 19 and driving pressure greater than or equal to 19, plateau pressure provided a slightly better prediction of outcome than driving pressure in both the derivation and validation cohorts (p < 0.0000001). Conclusions: Plateau pressure was slightly better than driving pressure in predicting hospital death in patients managed with lung-protective ventilation evaluated on standardized ventilator settings 24 hours after acute respiratory distress syndrome onset.

Looking for biological factors to predict the risk of active cytomegalovirus infection in non-immunosuppressed critically ill patients

The identification of non‐immunosuppressed critically ill patients most at risk for developing cytomegalovirus (CMV) reactivation is potentially of great clinical relevance. The current study was aimed at determining (i) whether single nucleotide polymorphisms in the genes coding for chemokine receptor 5 (CCR5), interleukin‐10 IL‐10), and monocyte chemoattractant protein‐1 (MCP‐1) have an impact on the incidence rate of active CMV infection, (ii) whether serum levels of CMV‐specific IgGs are associated with the risk of CMV reactivation, and (iii) whether detection of CMV DNA in saliva precedes that in the lower respiratory tract or the blood compartment. A total of 36 out of 78 patients (46%) developed an episode of active CMV infection. The incidence rate of active CMV infection was not significantly associated with any single nucleotide polymorphisms. A trend towards a lower incidence of active CMV infection (P = 0.06) was noted in patients harboring the IL10 C/C genotype. Patients carrying the CCR5 A/A genotype had high CMV DNA loads in tracheal aspirates. The serum levels of CMV IgGs did not differ significantly between patients with a subsequent episode of active CMV infection (median, 217 IU/mL) or without one (median, 494 IU/mL). Detection of CMV DNA in saliva did not usually precede that in plasma and/or tracheal aspirates. In summary, the analysis of single nucleotide polymorphisms in the IL10 and CCR5 genes might help to determine the risk of active CMV infection or the level of CMV replication within episodes, respectively, in non‐immunosuppressed critically ill patients. J. Med. Virol. 86:827–833, 2014.