C. Hernández-Gancedo

monitoring sedation in critically ill patients : bispectral index, Ramsay and observer scales

Background and objective: Sedation is commonly required by critically ill patients and inadequate sedation may be hazardous. Traditionally, subjective scales have been used for monitoring sedation. Bispectral index has been proposed, although its utility in the intensive care unit is debated. Our aim was to evaluate the depth of sedation in intubated surgical critically ill patients by means of two sedation scales (Ramsay and Observers Assessment of Alertness and Sedation) and bispectral index. Methods: Sedation was assessed prospectively in 50 postoperative intubated patients requiring at least 24 h of sedation (35 propofol, 15 midazolam/fentanyl), every 8 h for a 24 ‐h period. The bispectral index value recorded was the mean value obtained during a 10‐min observation period, whenever the quality signal index was above 75% and the electromyographic signal was below 25%. Results: Most of the patients (78%) were oversedated (bispectral index < 60). The three sedation scores (global data) correlated significantly (P < 0.001). This correlation was lost in the midazolam group in which the patients were also significantly more sedated than the propofol group (P = 0.001). The correlation between the bispectral index and the scales in the midazolam group reappeared when the measurements with a Ramsay = 6 or an Observers Assessment of Alertness and Sedation = 1 were excluded. Conclusions: Sedation should be monitored routinely in intensive care units. The Ramsay and the Observers Assessment of Alertness and Sedation scales showed equal efficacy. Bispectral index might prove useful for discriminating between deeper levels of sedation.

Micafungin pharmacokinetic/pharmacodynamic adequacy for the treatment of invasive candidiasis in critically ill patients on continuous venovenous haemofiltration

OBJECTIVES To explore the pharmacokinetics (PK) and pharmacodynamics (PD) of micafungin in patients undergoing continuous venovenous haemofiltration (CVVH). PATIENTS AND METHODS Ten patients receiving CVVH treated with 100 mg/day micafungin were included (April-December 2012). CVVH was performed using polyethersulphone or polysulphone haemofilters. Dialysis membranes were not changed on sampling days. On Days 1 and 2, blood samples from arterial pre-filter and venous post-filter ports and ultrafiltrate samples were collected at the start and end of the infusion and at 3, 5, 8, 18 and 24 h. Concentrations were determined using HPLC. Values for the area under the concentration-time curve (AUC0-24) were calculated. Monte Carlo simulations were performed using pre-filter and post-filter AUC0-24/MIC ratios on Days 1 and 2. The probability of target attainment (PTA) was calculated using AUC0-24/MIC cut-offs: 285 (C. parapsilosis), 3000 (all Candida spp.) and 5000 (non-parapsilosis Candida spp.). Cumulative fraction responses (CFRs) were calculated using EUCAST MIC distributions. RESULTS Mean post-filter AUC0-24 (mg·h/L) values were higher than pre-filter values on Day 1 (83.31 ± 15.87 versus 71.31 ± 14.24; P = 0.008) and Day 2 (119.01 ± 27.20 versus 104.54 ± 21.23; P = 0.005). PTAs were ≥90% for MICs of 0.125 mg/L (cut-off = 285), 0.016 mg/L (cut-off = 3000) and 0.008 mg/L (cut-off = 5000) on Day 1, and for MICs of 0.25 mg/L (cut-off = 285) and 0.016 mg/L (cut-off = 3000 and 5000) on Day 2, without differences between pre- and post-filter values. On Day 2, CFRs >90% were obtained for C. albicans (cut-off = 3000 and 5000) and C. glabrata (cut-off = 3000), but not for C. parapsilosis. CONCLUSIONS There was no removal of micafungin by CVVH or need for dose adjustment, and there was optimal PK/PD coverage for non-parapsilosis Candida and equivalence of pre- and post-filter PD.

Adjusting positive end-expiratory pressure and tidal volume in acute respiratory distress syndrome according to the pressure-volume curve.

Background:  Management of acute respiratory distress syndrome (ARDS) patients implies the selection of the adequate ventilatory parameters, essentially PEEP and tidal volume (Vt), to prevent ventilator‐induced lung injury. These parameters should be reset as the lung injury evolves. Among the different methods proposed for the adjustment of the ventilator, the measurement of the P–V curve has emerged as a useful, although debated, tool. Our aim has been to study the relationship between the different inflection points of the P–V curve in ARDS patients, and to assess the changes in the empiric PEEP and Vt (PEEPemp, Vtemp) following its use.

Pressure-volume curve variations after a recruitment manoeuvre in acute lung injury/ARDS patients: implications for the understanding of the inflection points of the curve.

Background and objective: Although the pressure‐volume (P‐V) curve has been proposed in the management of mechanically ventilated patients, its interpretation remains unclear. Our aim has been to study the variations of the P‐V curve after a recruitment manoeuvre (RM). Our hypothesis was that the lower inflection point (LIP) represents the presence of compressive atelectases, so it should not change after lung recruitment, while the upper inflection point (UIP) reflects reabsorptive atelectases, and an effective recruitment should result in changes at this level. Methods: Two P‐V curves (quasi‐static method) separated by an RM (40 cmH2O, two consecutive manoeuvres) were plotted in 35 postoperative patients with criteria of acute lung injury/acute respiratory distress syndrome (ARDS). LIP, UIP and expiratory inflection point (EIP) were defined as the first point where the curve consistently starts to separate from the line. Results: One to six measurements were obtained per patient (73 procedures). Neither the lower nor the EIPs varied significantly after the RM (P = 0.11 and 0.35, respectively). An UIP was observed in 18 curves (25%) before the RM and disappeared on nine occasions after the recruitment. Similar results were obtained when first measurements only were analysed, and when the cause (pulmonary vs. extrapulmonary), severity of lung injury or duration of mechanical ventilation at first measurement were studied. Conclusions: An RM does not modify the LIP significantly, but induces the disappearance of the UIP in 50% of the cases in which this point is found.

Pharmacokinetics/pharmacodynamics of micafungin in a surgical critically ill patient during extracorporeal carbon dioxide removal and continuous renal replacement therapy

Multiple organ failure is the leading cause ofmorbidity andmortality in the intensive care unit (ICU) and may significantly affect pharmacokinetics of different drugs commonly used in critically ill patients. Organ support techniques as renal replacement therapy (RRT) and extracorporealmembrane oxygenation (ECMO) further increase the pharmacokinetic variability in this population. These facts are important because extracorporeal supporting techniques are increasingly used in the ICU. An alternate less complex technique for lung assistance is the pumpless extracorporeal interventional lung assist (iLA) that provides impressive carbon dioxide elimination and can be used as adjunct to mechanical ventilation affording optimized lung-protective ventilation strategies [1]. In contrast to RRT or ECMO, no pharmacokinetic/pharmacodynamic (PK/PD) data of any drugs have been described in patients on iLA. Pharmacokinetic changes attributed to ECMO have been reported based on increased volumeof distribution, changes in drug clearance, and alterations due to binding to various extracorporeal circuit components in a drug-dependent manner [2,3]. In this sense, increased lipophilicity has been associated with increased absorption to the ECMO circuit [2]; echinocandins and voriconazole, which are highly protein bound and lipophilic, are predisposed to high adhesion to the ECMO circuit [2]. Because invasive candidiasis can be a devastating complication of ECMO [2] and probably of others as iLA, understanding pharmacokinetics of antifungals is crucial for critical care medicine. We describe pharmacokinetics of micafungin in a surgical critical patient on RRT and iLA due to multiple organ failure. A 23-year-old oncological male patient who had undergone esophageal coloplasty, colectomy, left colon coloplasty, and gastrostomy with esophagus colon, colon jejunum, and colocolo anastomoses was admitted to the surgical ICU. The patient had been on parenteral nutrition for years due to an esophagealfistula and presented a bodyweight of 48 kg. The patient developed multiorgan failure requiring RRT (continuous

Variaciones hemodinámicas inducidas por la realización de una curva presión-volumen y una maniobra de reclutamiento alveolar en pacientes con síndrome de distrés respiratorio agudo

Summary OBJECTIVES: The plotting of pressure-volume curves and the performance of alveolar recruitment maneuvers are common practices in the care of patients with adult respiratory distress syndrome (ARDS), even though potentially harmful hemodynamic effects are associated with sustaining a high intrathoracic pressure. Our aim was to analyze hemodynamic and ventilatory changes related to these 2 maneuvers and to assess the short-term effectiveness of recruitment. PATIENTS AND METHODS: The patients had ARDS and were being monitored with a catheter connected to a PiCCO system. All measurements were taken in sinus rhythm and with adequate vascular filling. Values recorded during plotting of the quasistatic pressure-volume curve and the recruitment maneuver (sustained airway pressure of 40 cm H2O) were the cardiac index, mean arterial pressure, heart rate, systolic volume index, and oxygen saturation (SpO2). Blood gas measurements were recorded before the maneuvers and 15 minutes afterwards. RESULTS: All parameters decreased significantly in the 14 patients studied. The mean (SD) maximum decreases, from which all patients recovered within 2 minutes, were as follows: cardiac index, 26% (16%); mean arterial pressure, 6% (6%); heart rate, 4% (5%), systolic volume index, 21% (15%); and SpO2, 3% (3%). Significant increases in PaO2 (7% [6%]) and the ratio of PaO2 to the fraction of inspired oxygen were recorded after the recruitment maneuver (P=.016 and P=.014, respectively), but the changes were not clinically significant. CONCLUSIONS: The hemodynamic disturbances associated with the alveolar recruitment maneuver based on sustaining a high end-expiratory pressure and the minor improvement in oxygenation achieved as a result suggest that the routine use of that maneuver in ARDS patients is of questionable value.

Risk factors for acute kidney injury in critically ill patients with complicated intra-abdominal infection

Purpose: The aim was to determine the factors related to acute kidney injury (AKI) in surgical septic patients with complicated intra‐abdominal infection (CIAI) and mortality associated to AKI. Methods: An observational study was performed in patients with CIAI requiring surgery and ICU admission (June 2011‐June 2013). Factors at admission associated with developing of AKI and renal replacement therapy (RRT) and association between mortality and AKI and RRT were studied. Results: A total of 114 patients were included. Developing of AKI was independently associated with the sequential organ failure assessment (SOFA) score (odds ratio [OR], 1.570; 95% confidence interval [CI], 1.286‐2.016) and creatinine at admission (OR for 0.1 units, 1.560; 95% CI, 1.296‐1.990). Renal replacement therapy was independently associated with arterial hypertension (OR, 4.896; 95% CI, 1.501‐15.971) and SOFA (OR, 1.713; 95% CI, 1.377‐2.132). In another model with more predictive capacity, the number of previous medications that may alter renal function (OR, 3.732; 95% CI, 1.923‐8.383) and SOFA (OR, 1.860; 95% CI, 1.469‐2.541) were related to RRT. Both AKI and RRT were related to intensive care unit (P = .014 and P < .001, respectively) and 28‐day mortality (P = .045 and P < .001, respectively). Conclusions: Acute kidney injury in patients with CIAI is clearly associated with SOFA and creatinine at admission. Severe AKI with RRT need is highly associated with both previous arterial hypertension and the number of previous medications potentially affecting renal function.

Severe cefepime-induced status epilepticus treated with haemofiltration.

Neurotoxicity caused by cefepime may occur predominantly in patients with impaired renal function. A case of a cefepime-induced non-convulsive status epilepticus (NCSE) is presented. A 65-year-old woman suffered a severe NCSE due to cefepime in the presence of acute renal failure, requiring coma induction with sodium thiopental. A serious interaction between valproic acid (VPA) and meropenem was also produced after changing cefepime to meropenem. Continuous veno-venous haemofiltration was employed to improve cefepime clearance, and the patient progressively regained her previous mental condition. In conclusion, the cefepime dose must be adjusted according to renal function in order to avoid toxicity in patients with renal failure. Electroencephalogram should be considered in cases of acute confusional state in patients receiving cefepime, to achieve early detection of NCSE. Continuous renal replacement therapy may be successfully employed in severe cases in order to accelerate cefepime removal. Likewise, meropenem should not be used concomitantly with VPA.