Ceftolozane/tazobactam for the treatment of multidrug resistant Pseudomonas aeruginosa: experience from the Balearic Islands.

A prospective, descriptive observational study of consecutive patients treated with ceftolozane/tazobactam in the reference hospital of the Balearic Islands (Spain), between May 2016 and September 2017, was performed. Demographic, clinical, and microbiological variables were recorded. The later included resistance profile, molecular typing, and whole genome sequencing of isolates showing resistance development. Fifty-eight patients were treated with ceftolozane/tazobactam. Thirty-five (60.3%) showed respiratory tract infections, 21 (36.2%) received monotherapy, and 37 (63.8%) combined therapy for ≥ 72 h, mainly with colistin (45.9%). In 46.6% of the patients, a dose of 1/0.5 g/8 h was used, whereas 2/1 g/8 h was used in 41.4%. In 56 of the cases (96.6%), the initial Pseudomonas aeruginosa isolates recovered showed a multidrug resistant (MDR) phenotype, and 50 of them (86.2%) additionally met the extensively drug resistant (XDR) criteria and were only susceptible colistin and/or aminoglycosides (mostly amikacin). The epidemic high-risk clone ST175 was detected in 50% of the patients. Clinical cure was documented in 37 patients (63.8%) and resistance development in 8 (13.8%). Clinical failure was associated with disease severity (SOFA), ventilator-dependent respiratory failure, XDR profile, high-risk clone ST175, negative control culture, and resistance development. In 6 of the 8 cases, resistance development was caused by structural mutations in AmpC, including some mutations described for the first time in vivo, whereas in the other 2, by mutations in OXA-10 leading to the extended spectrum OXA-14. Although further clinical experience is still needed, our results suggest that ceftolozane/tazobactam is an attractive option for the treatment of MDR/XDR P. aeruginosa infections.

Genomics and Susceptibility Profiles of Extensively Drug-Resistant Pseudomonas aeruginosa Isolates from Spain.

This study assessed the molecular epidemiology, resistance mechanisms, and susceptibility profiles of a collection of 150 extensively drug-resistant (XDR) Pseudomonas aeruginosa clinical isolates obtained from a 2015 Spanish multicenter study, with a particular focus on resistome analysis in relation to ceftolozane-tazobactam susceptibility. Broth microdilution MICs revealed that nearly all (>95%) of the isolates were nonsusceptible to piperacillin-tazobactam, ceftazidime, cefepime, aztreonam, imipenem, meropenem, and ciprofloxacin. Most of them were also resistant to tobramycin (77%), whereas nonsusceptibility rates were lower for ceftolozane-tazobactam (31%), amikacin (7%), and colistin (2%). Pulsed-field gel electrophoresis-multilocus sequence typing (PFGE-MLST) analysis revealed that nearly all of the isolates belonged to previously described high-risk clones. Sequence type 175 (ST175) was detected in all 9 participating hospitals and accounted for 68% (n = 101) of the XDR isolates, distantly followed by ST244 (n = 16), ST253 (n = 12), ST235 (n = 8), and ST111 (n = 2), which were detected only in 1 to 2 hospitals. Through phenotypic and molecular methods, the presence of horizontally acquired carbapenemases was detected in 21% of the isolates, mostly VIM (17%) and GES enzymes (4%). At least two representative isolates from each clone and hospital (n = 44) were fully sequenced on an Illumina MiSeq. Classical mutational mechanisms, such as those leading to the overexpression of the ß-lactamase AmpC or efflux pumps, OprD inactivation, and/or quinolone resistance-determining regions (QRDR) mutations, were confirmed in most isolates and correlated well with the resistance phenotypes in the absence of horizontally acquired determinants. Ceftolozane-tazobactam resistance was not detected in carbapenemase-negative isolates, in agreement with sequencing data showing the absence of ampC mutations. The unique set of mutations responsible for the XDR phenotype of ST175 clone documented 7 years earlier were found to be conserved, denoting the long-term persistence of this specific XDR lineage in Spanish hospitals. Finally, other potentially relevant mutations were evidenced, including those in penicillin-binding protein 3 (PBP3), which is involved in ß-lactam (including ceftolozane-tazobactam) resistance, and FusA1, which is linked to aminoglycoside resistance.

Hyperinflammatory Immune Response in COVID-19: Host Genetic Factors in Pyrin Inflammasome and Immunity to Virus in a Spanish Population from Majorca Island.

The hyperinflammatory response caused by SARS-CoV-2 infection contributes to its severity, and many critically ill patients show features of cytokine storm (CS) syndrome. We investigated, by next-generation sequencing, 24 causative genes of primary immunodeficiencies whose defect predisposes to CS. We studied two cohorts with extreme phenotypes of SARS-CoV-2 infection: critical/severe hyperinflammatory patients (H-P) and asymptomatic patients (AM-risk-P) with a high risk (older age) to severe COVID-19. To explore inborn errors of the immunity, we investigated the presence of pathogenic or rare variants, and to identify COVID-19 severity-associated markers, we compared the allele frequencies of common genetic polymorphisms between our two cohorts. We found: 1 H-P carries the likely pathogenic variant c.887-2 A>C in the IRF7 gene and 5 H-P carries variants in the MEFV gene, whose role in the pathogenicity of the familial Mediterranean fever (FMF) disease is controversial. The common polymorphism analysis showed three potential risk biomarkers for developing the hyperinflammatory response: the homozygous haplotype rs1231123A/A-rs1231122A/A in MEFV gene, the IFNAR2 p.Phe8Ser variant, and the CARMIL2 p.Val181Met variant. The combined analysis showed an increased risk of developing severe COVID-19 in patients that had at least one of our genetic risk markers (odds ratio (OR) = 6.2 (95% CI) (2.430-16.20)).

Ventilatory support in critically ill hematology patients with respiratory failure.

INTRODUCTION: Hematology patients admitted to the ICU frequently experience respiratory failure and require mechanical ventilation. Noninvasive mechanical ventilation (NIMV) may decrease the risk of intubation, but NIMV failure poses its own risks. METHODS: To establish the impact of ventilatory management and NIMV failure on outcome, data from a prospective, multicenter, observational study were analyzed. All hematology patients admitted to one of the 34 participating ICUs in a 17-month period were followed up. Data on demographics, diagnosis, severity, organ failure, and supportive therapies were recorded. A logistic regression analysis was done to evaluate the risk factors associated with death and NIVM failure. RESULTS: Of 450 patients, 300 required ventilatory support. A diagnosis of congestive heart failure and the initial use of NIMV significantly improved survival, whereas APACHE II score, allogeneic transplantation, and NIMV failure increased the risk of death. The risk factors associated with NIMV success were age, congestive heart failure, and bacteremia. Patients with NIMV failure experienced a more severe respiratory impairment than did those electively intubated. CONCLUSIONS: NIMV improves the outcome of hematology patients with respiratory insufficiency, but NIMV failure may have the opposite effect. A careful selection of patients with rapidly reversible causes of respiratory failure may increase NIMV success.

Potential effects of corticosteroids on physiological dead-space fraction in acute respiratory distress syndrome.

BACKGROUND: Increased dead-space fraction is common in patients with persistent acute respiratory distress syndrome (ARDS). We evaluated the changes in the oxygenation and dead-space fraction in patients with persistent ARDS after corticosteroid therapy. METHODS: This was a non-randomized non-placebo, controlled observational study including 19 patients with persistent ARDS treated with corticosteroids. We measured P(aO(2))/F(IO(2)) and dead-space fraction at days 0, 4, and 7 after corticosteroids treatment (methylprednisolone) initiation. Patients were classified in intermediate group when corticosteroids were initiated between days 8-14 after ARDS onset, and in late group when initiated after 14 days. RESULTS: Mean time from the diagnosis of the ARDS to methylprednisolone treatment was 11 ± 2 days in the intermediate group (10 patients) and 21 ± 8 days in the late group (9 patients). When comparing days 0, 4, and 7 after methylprednisolone treatment, we found an increase in the P(aO(2))/F(IO(2)) (145 ± 64 mm Hg, 190 ± 68 mm Hg, and 226 ± 84 mm Hg, respectively, P < .001) and a decrease in the physiological dead-space fraction (0.66 ± 0.10, 0.58 ± 0.12, and 0.53 ± 0.11, respectively, P < .001). No differences were found between the intermediate and late groups. CONCLUSIONS: In patients with persistent ARDS, the increase in oxygenation was accompanied by a decrease in the dead-space fraction after a few days of corticosteroid treatment. To confirm potential benefit of corticosteroids on physiological parameters and mortality will require a powered randomized placebo controlled trial.

Fluconazole-resistant Candida parapsilosis clonally related genotypes: first report proving the presence of endemic isolates harbouring the Y132F ERG11 gene substitution in Spain.

OBJECTIVES: We report here for the first time the presence of Candida parapsilosis isolates harbouring the Y132F ERG11 gene substitution in patients admitted to a Spanish hospital. METHODS: We studied the available (n = 104) C parapsilosis isolates from patients admitted to the Son Espases reference hospital in the Balearic Islands from 1 April 2019 to 30 November 2020. Isolates were sourced from 70 patients: catheter (n = 41), blood cultures (n = 37), lower respiratory tract (n = 15), intra-abdominal (n = 8), and other samples (n = 3). Isolates were genotyped and tested for antifungal susceptibilities to amphotericin B, triazoles, anidulafungin, and micafungin using EUCAST E.Def 7.3.2. The ERG11 gene was sequenced in fluconazole-resistant isolates. RESULTS: Among the 104 isolates, fluconazole and voriconazole resistance was found in 87 (84%) and 30 (29%) isolates, respectively; all isolates were fully susceptible to echinocandins and amphotericin B. All fluconazole-resistant isolates harboured the Y132F substitution in the ERG11 gene and were grouped into 11 clonally related genotypes. A genotype accounted for 70% (61/87) of fluconazole-resistant isolates. Genotypes involving the fluconazole-resistant isolates were different from those found in the remaining fluconazole-susceptible genotypes. Fifty-six patients harboured fluconazole-resistant genotypes, and 35 of the 56 had candidaemia (48%), abdominal candidiasis (17%), or other forms of candidiasis (35%). Only 20% of the study patients infected by fluconazole-resistant genotypes had a history of azole use. DISCUSSION: Fluconazole resistance in C parapsilosis isolates from patients admitted to this reference hospital is not attributable to prior azole use, but rather to the presence of a group of fluconazole-resistant C parapsilosis genotypes that have become endemic.

CO2 response and duration of weaning from mechanical ventilation.

BACKGROUND: The CO2 response test measures the hypercapnic drive response (which is defined as the ratio of the change in airway-occlusion pressure 0.1 s after the start of inspiratory flow [ΔP(0.1)] to the change in P(aCO2) [ΔP(aCO2)]), and the hypercapnic ventilatory response (which is defined as the ratio of the change in minute volume to ΔP(aCO2)). OBJECTIVE: In mechanically ventilated patients ready for a spontaneous breathing trial, to investigate the relationship between CO2 response and the duration of weaning. METHODS: We conducted the CO2 response test and measured maximum inspiratory pressure (P(Imax)) and maximum expiratory pressure (P(Emax)) in 102 non-consecutive ventilated patients. We categorized the patients as either prolonged weaning (weaning duration > 7 d) or non-prolonged weaning (≤ 7 d). RESULTS: Twenty-seven patients had prolonged weaning. Between the prolonged and non-prolonged weaning groups we found differences in hypercapnic drive response (0.22 ± 0.16 cm H2O/mm Hg vs 0.47 ± 0.22 cm H2O/mm Hg, respectively, P < .001) and hypercapnic ventilatory response (0.25 ± 0.23 L/min/mm Hg vs 0.53 ± 0.33 L/min/mm Hg, respectively, P < .001). The optimal cutoff points to differentiate between prolonged and non-prolonged weaning were 0.19 cm H2O/mm Hg for hypercapnic drive response, and 0.15 L/min/mm Hg for hypercapnic ventilatory response. Assessed with the Cox proportional hazards model, both hypercapnic drive response and hypercapnic ventilatory response were independent variables associated with the duration of weaning. The hazard ratio of weaning success was 16.7 times higher if hypercapnic drive response was > 0.19 cm H2O/mm Hg, and 6.3 times higher if hypercapnic ventilatory response was > 0.15 L/min/mm Hg. Other variables (P(0.1), P(Imax), and P(Emax)) were not associated with the duration of the weaning. CONCLUSIONS: Decreased CO2 response, as measured by hypercapnic drive response and hypercapnic ventilatory response, are associated with prolonged weaning.

Hypoxic hepatitis in critically ill patients: incidence, etiology and risk factors for mortality.

PURPOSE: Hypoxic hepatitis may be induced by hemodynamic instability or arterial hypoxemia in critically ill patients. We investigated the incidence, etiology, association with systemic ischemic injury and risk factors for mortality in this population. METHODS: Retrospective analysis of patients with hypoxic hepatitis admitted to a multidisciplinary intensive care unit (ICU) of a university hospital. Hypoxic hepatitis was defined as the existence of a compatible clinical setting (cardiocirculatory failure or arterial hypoxemia) and aminotransferase levels higher than 1000 IU/L. RESULTS: During the 8-year study period, 182 out of the 7674 patients admitted presented hypoxic hepatitis (2.4%). The most common cause was septic shock. The rate of in-hospital mortality in hypoxic hepatitis was 61.5% (112 patients), and was higher in patients with septic shock (83.3%) and cardiac arrest (77.7%). Ischemic pancreatitis (25.6%), rhabdomyolysis (41.2%) and renal failure (67.2%) were common in these patients. Risk factors of mortality were prolonged INR (p = 0.005), need for renal replacement therapy (p = 0.001) and septic shock (p = 0.005). CONCLUSIONS: Hypoxic hepatitis was not a rare condition, and was frequently accompanied by multiorgan injury, with high mortality. Risk factors for increased mortality were prolonged INR, need for renal replacement therapy, and septic shock.

Hypercapnic respiratory failure in obesity-hypoventilation syndrome: CO2 response and acetazolamide treatment effects.

OBJECTIVE: In obesity-hypoventilation-syndrome patients mechanically ventilated for hypercapnic respiratory failure we investigated the relationship between CO2 response, body mass index, and plasma bicarbonate concentration, and the effect of acetazolamide on bicarbonate concentration and CO2 response. METHODS: CO2 response tests and arterial blood gas analysis were performed in 25 patients ready for a spontaneous breathing test, and repeated in a subgroup of 8 patients after acetazolamide treatment. CO2 response test was measured as (1) hypercapnic drive response (the ratio of the change in airway occlusion pressure 0.1 s after the start of inspiratory flow to the change in P(aCO2)), and (2) hypercapnic ventilatory response (the ratio of the change in minute volume to the change in P(aCO2)). RESULTS: We did not find a significant relationship between CO2 response and body mass index. Patients with higher bicarbonate concentration had a more blunted CO2 response. Grouping the patients according to the first, second, and third tertiles of the bicarbonate concentration, the hypercapnic drive response was 0.32 ± 0.17 cm H2O/mm Hg, 0.22 ± 0.15 cm H2O/mm Hg, and 0.10 ± 0.06 cm H2O/mm Hg, respectively (P = .01), and hypercapnic ventilatory response was 0.46 ± 0.23 L/min/mm Hg, 0.48 ± 0.36 L/min/mm Hg, and 0.22 ± 0.16 L/min/mm Hg, respectively (P = .04). After acetazolamide treatment, bicarbonate concentration was reduced by 8.4 ± 3.0 mmol/L (P = .01), and CO2 response was shifted to the left, with an increase in hypercapnic drive response, by 0.14 ± 0.16 cm H2O/mm Hg (P = .02), and hypercapnic ventilatory response, by 0.11 ± 0.22 L/min/mm Hg (P = .33). CONCLUSIONS: Patients with obesity-hypoventilation syndrome and higher bicarbonate concentrations had a more blunted CO2 response. Body mass index was not related to CO2 response. Acetazolamide decreased bicarbonate concentration and increased CO2 response.

Prognostic value of the pulmonary dead-space fraction during the early and intermediate phases of acute respiratory distress syndrome.

BACKGROUND: Little is known about the alveolar dead-space fraction after the first week of acute respiratory distress syndrome (ARDS). We measured the dead-space fraction in the early phase (first week) and the intermediate phase (second week) of ARDS, and evaluated the association of dead-space fraction with mortality. METHODS: We prospectively measured dead-space fraction and other variables in 80 intubated patients during the early phase of ARDS and in 49 patients during the intermediate phase. We used multiple logistic regression analysis to evaluate data. The primary outcome was in-hospital mortality. RESULTS: In the early and intermediate phases the dead-space fraction was higher in patients who died than among those who survived (dead-space fraction 0.64 +/- 0.09 vs 0.53 +/- 0.11, P < .001, and 0.62 +/- 0.09 vs 0.50 +/- 0.10, P < .001, respectively). In both the early and intermediate phases the dead-space fraction was independently associated with a greater risk of death. For every dead-space-fraction increase of 0.05 the odds of death increased by 59% in the early phase (odds ratio 1.59, 95% confidence interval 1.18-2.16, P = .003) and by 186% in the intermediate phase (odds ratio 2.87, 95% confidence interval 1.36-6.04, P = .005). Age and Sequential Organ Failure Assessment score were also independently associated with a greater risk of death in both phases. CONCLUSIONS: Increased alveolar dead-space fraction in the early and intermediate phases of ARDS is associated with a greater risk of death.

Incidence and outcome of ischemic hepatitis complicating septic shock.

AIM: The specific incidence of ischemic hepatitis in septic shock patients remains unknown. The aim of this study was to evaluate the incidence of ischemic hepatitis in septic shock and its relationship with mortality. METHODS: We retrospectively studied 181 patients with septic shock admitted to the intensive care unit (ICU). We defined ischemic hepatitis as having a value of serum aminotransferases equal to or higher than 1000 IU/L. We recorded the age, sex, comorbidity, site of infection, the Sequential Organ Failure Assessment (SOFA) score on admission to the ICU, maximum SOFA score and inadequate antibiotic therapy. RESULTS: Twenty-five (13.8%) patients developed ischemic hepatitis. In-hospital mortality was 57% (103 patients). In the ischemic hepatitis group, mortality increased up to 84.0% (21 patients) compared with 52.6% (82 patients) in patients without ischemic hepatitis (control group) (odds ratio [OR]: 4.7; 95% confidence interval [CI]: 1.6-14.4; P = 0.003). The development of ischemic hepatitis, age, maximum SOFA score and inadequate antibiotic therapy were independently associated with an increased risk of death. The odds of death increased by 247% in ischemic hepatitis (OR: 3.47; 95% CI: 1.02-11.8; P = 0.047). CONCLUSION: Ischemic hepatitis is a common complication in septic shock patients, associated with a high mortality.

The Trends in Opioid Use in Castile and Leon, Spain: A Population-Based Registry Analysis of Dispensations in 2015 to 2018.

Opioids are driving-impairing medicines (DIM). To assess the evolution and trends of opioid analgesics use between 2015 and 2018 in Castile and Leon (Spain), a population-based registry study was conceived. The length of opioid use and its concomitant use with other DIMs were studied. Analyses were done considering age and gender distributions. Adjusted consumption for licensed drivers is also presented. Of the 5 million dispensations recorded between 2015 and 2018, opioid analgesics were dispensed to 11.44% of the general population and 8.72% of vehicle drivers. Increases among daily users (2.6 times higher) and chronic users (1.5% higher) were noted, supporting the overall increase in opioid use (1.5%). The use of multiple drugs including other DIMs was a common finding (mean ± SD, 2.54 ± 0.01). Acute use (5.26%) and chronic use (3.20%) were also frequent. Formulations combining opioid analgesics with nonopioid analgesics were preferred. The use of opioids increased in Spain between 2015 and 2018. Concomitant use with other DIMS especially affects women and the elderly. Frequent use of opioid analgesics with other DIMs is a serious problem for drivers and increases the risk of accidents. Promoting safe driving should be a main objective of health authorities, to be achieved by developing and implementing educational activities for healthcare professionals and patients.

Hypercapnia test as a predictor of success in spontaneous breathing trials and extubation.

BACKGROUND: The ventilatory capacity of the respiratory neuromuscular system can be studied with the hypercapnia test. OBJECTIVE: To determine whether decreased response to the hypercapnia test is associated with failure to pass a spontaneous breathing trial (SBT) or extubation failure. METHODS: We studied 103 intubated patients ready for SBT. We used a hypercapnia test in which we approximately doubled the dead space and thus caused re-inhalation of expired air. We calculated 3 ratios: the ratio of P(0.1) (airway occlusion pressure 0.1 s after the onset of inspiratory effort) during hypercapnia test to baseline P(0.1); the ratio of the change in minute volume [DeltaV(E)] to the change in P(aCO(2)) (we call this ratio the hypercapnic ventilatory response); and the ratio of the change in P(0.1) [DeltaP(0.1)] to the change P(aCO(2)) (we call this ratio the hypercapnic-respiratory-drive response). RESULTS: Thirty-six patients failed the SBT, and 11 patients failed extubation. The mean values for the SBT/extubation-success group, the extubation-failure group, and the SBT-failure group, respectively, were: ratio of hypercapnia-test P(0.1) to baseline P(0.1): 4.3 +/- 2.7, 3.7 +/- 1.3, and 3.0 +/- 1.8 (P = .03); hypercapnic ventilatory response: 0.60 +/- 0.35 L/min/mm Hg, 0.50 +/- 0.26 L/min/mm Hg, and 0.31 +/- 0.21 L/min/mm Hg (P < .001); hypercapnic respiratory-drive response: 0.48 +/- 0.24 cm H(2)O/mm Hg, 0.42 +/- 0.19 cm H(2)O/mm Hg, and 0.27 +/- 0.15 cm H(2)O/mm Hg (P < .001). For predicting SBT/extubation success, the sensitivities and specificities, respectively, were: ratio of hypercapnia-test P(0.1) to baseline P(0.1) 0.80 and 0.47; hypercapnic ventilatory response 0.86 and 0.53; hypercapnic respiratory-drive response 0.82 and 0.55. CONCLUSIONS: The SBT/extubation-failure patients had less response to the hypercapnia test than did the SBT/extubation-success patients, and the hypercapnia test was not useful in predicting SBT or extubation success.

Successful weaning from continuous renal replacement therapy. Associated risk factors.

PURPOSE: To identify risk factors of successful continuous renal replacement therapy (CRRT) weaning and to evaluate the effect of furosemide in the recovery of urine output after CRRT stop. MATERIALS AND METHODS: Retrospective, observational study of critical patients treated with CRRT. Weaning tests (WT) were classified in two groups: successful (urine output was recovered and CRRT was not required again) and failed (CRRT was required again). A multiple logistic regression model was used to identify risk factors of successful CRRT WT. The prediction ability was assessed with the area under the receiver operating characteristic curves (AUC-ROC). RESULTS: Eighty-six patients underwent 101 CRRT WT. The multivariate model identified that the risk factors of successful CRRT weaning were sex and 6h-urine output after CRRT stop. The AUC-ROC was 0.81 (0.72-0.90) for 6h-urine output before and 0.91 (0.84-0.96) for 6h-urine output after CRRT stop. The AUC-ROC for 6h-urine output after WT to predict successful CRRT weaning were 0.94 (0.88-1.0) in patients who received furosemide and 0.85 (0.72-0.99) in patients who did not. CONCLUSIONS: Urine output after CRRT stop was the main risk factor of successful CRRT weaning. Administration of furosemide increased the strength of this association.

Hyperlactatemia in ICU patients: Incidence, causes and associated mortality.

PURPOSE: To describe the incidence, causes and associated mortality of hyperlactatemia in critically ill patients and to evaluate the association between lactate clearance and in-hospital survival. METHODS: Retrospective cohort study of patients with hyperlactatemia admitted to the ICU. Hyperlactatemia was defined as a blood lactate concentration ≥5mmol/L and high-grade hyperlactatemia a lactate level ≥10mmol/L. Lactate clearance was calculated as the percentage of decrease in lactate concentration from the peak value. RESULTS: Of 10,123 patients, 1373 (13.6%) had lactate concentration ≥5mmol/L, and 434(31.6%) of them had ≥10mmol/L. The most common causes of hyperlactatemia were sepsis/septic shock and post-cardiac surgery. An association was found between lactate concentration and in-hospital mortality (p<0.001). The area under the receiver-operating-characteristics (ROC) of lactate concentration and the optimal cut off to predict mortality were 0.72 (0.70-0.75) and 8.6mmol/L, respectively. ROC analysis for lactate clearance to predict in-hospital survival showed that the best area under the curve was obtained at 12h: 0.67 (95% confidence interval 0.59-0.75). CONCLUSIONS: Hyperlactatemia was common and associated with a high mortality in critically ill patients. Lactate clearance had limited utility for predicting in-hospital survival.

Role of Respiratory Drive in Hyperoxia-Induced Hypercapnia in Ready-to-Wean Subjects With COPD.

BACKGROUND: Hyperoxia-induced hypercapnia in subjects with COPD is mainly explained by alterations in the ventilation/perfusion ratio. However, it is unclear why respiratory drive does not prevent CO2 retention. Some authors have highlighted the importance of respiratory drive in CO2 increases during hyperoxia. The aim of the study was to examine the effects of hyperoxia on respiratory drive in subjects with COPD. METHODS: Fourteen intubated, ready-to-wean subjects with COPD were studied during normoxia and hyperoxia. A CO2 response test was then performed with the rebreathing method to measure the hypercapnic drive response, defined as the ratio of change in airway-occlusion pressure 0.1 s after the start of inspiratory flow (ΔP(0.1)) to change in P(aCO2) (ΔP(aCO2)), and the hypercapnic ventilatory response, defined as the ratio of change in minute volume (ΔV̇(E)) to ΔP(aCO2). RESULTS: Hyperoxia produced a significant increase in P(aCO2) (55 ± 9 vs 58 ± 10 mm Hg, P = .02) and a decrease in pH (7.41 ± 0.05 vs 7.38 ± 0.05, P = .01) compared with normoxia, with a non-significant decrease in V̇(E) (9.9 ± 2.9 vs 9.1 ± 2.3 L/min, P = .16) and no changes in P(0.1) (2.85 ± 1.40 vs 2.82 ± 1.16 cm H2O, P = .97) The correlation between hyperoxia-induced changes in V̇(E) and P(aCO2) was r(2) = 0.38 (P = .02). Median ΔP(0.1)/ΔP(aCO2) and ΔV̇(E)/ΔP(aCO2) did not show significant differences between normoxia and hyperoxia: 0.22 (0.12-0.49) cm H2O/mm Hg versus 0.25 (0.14-0.34) cm H2O/mm Hg (P = .30) and 0.37 (0.12-0.54) L/min/mm Hg versus 0.35 (0.12-0.96) L/min/mm Hg (P = .20), respectively. CONCLUSIONS: In ready-to-wean subjects with COPD exacerbations, hyperoxia is followed by an increase in P(aCO2), but it does not significantly modify the respiratory drive or the ventilatory response to hypercapnia.

Role of Elevated Aminotransferases in ICU Patients with Rhabdomyolysis.

To evaluate whether patients with rhabdomyolysis and serum alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) higher than 1000 IU/L had higher mortality that patients with low aminotransferases. Retrospective analysis of intensive care unit patients with rhabdomyolysis [creatine kinase (CK) higher than 5000 IU/L]. Patients were classified in two groups: low aminotransferases group, when AST and ALT were equal or lower to 1000 IU/L, and elevated aminotransferases group, when AST or ALT was above 1000 IU/L. Forty-six out of 189 patients included in the analysis (24.3%) had elevated aminotransferases. The mortality of patients with rhabdomyolysis was 25.9 per cent, being higher in patients with elevated aminotransferases compared with patients with low aminotransferases (60.9% vs 14.7%; P < 0.001). Mortality stratified by quartiles of CK in patients with low aminotransferases was independent of the level of CK (P = 0.67). Logistic regression analysis showed that the independent variables associated with mortality were Simplified Acute Physiology Score II [1.11 (1.07-1.16) for each point of increase, P < 0.001], the international normalized ratio value [4.2 (1.6-10.7) for each point of increase, P = 0.003], and the need of renal replacement therapy [5.4 (1.7-17.2), P = 0.004]. Patients with rhabdomyolysis with elevated serum aminotransferases had higher mortality than patients with low serum aminotransferase levels.

A SIMPLIFIED EQUATION FOR TOTAL ENERGY EXPENDITURE IN MECHANICALLY VENTILATED CRITICALLY ILL PATIENTS.

INTRODUCTION: "tight calorie control" concept arose to avoid over- and under-feeding of patients. OBJECTIVE: to describe and validate a simplified predictive equation of total energy expenditure (TEE) in mechanically ventilated critically ill patients. METHODS: this was a secondary analysis of measurements of TEE by indirect calorimetry in critically ill patients. Patients were allocated in a 2:1 form by a computer package to develop the new predictive equation TEE (prediction cohort) and the validation cohort. Indirect calorimetry was performed with three different calorimeters: the Douglas-bag, a metabolic computer and the CalorimetR. We developed a new TEE predictive equation using measured TEE (in kcal/kg/d) as dependent variable and as independent variables different factors known to influence energy expenditure: age, gender, body mass index (BMI) and type of injury. RESULTS: prediction cohort: 179 patients. Validation cohort: 91 patients. The equation was: TEEPE (kcal/Kg/d) = 33 - (3 x A) - (3 x BMI) - (1 x G). Where: A (age in years): ≤ 50 = 0; > 50 = 1. BMI (Kg/m2): 18.5 - 24.9 = 0; 25 - 29.9 = 1; 30 - 34.9 = 2; 35 - 39.9 = 3. G (gender): male = 0; female = 1. The bias (95% CI) was -0.1 (-1.0 - 0.7) kcal/kg/d and the limits of agreement (} 2SD) were -8.0 to 7.8 kcal/kg/d. Predicted TEE was accurate (within 85% to 115%) in 73.6% of patients. CONCLUSION: the new predictive equation was acceptable to predict TEE in clinical practice for most mechanically ventilated critically ill patients.

Introducción: el concepto de "control calorico estricto" surgio para evitar la excesiva y la deficiente nutricion de los pacientes. Objetivo: describir y validar una ecuacion simplificada para el calculo del gasto energetico total (GET) en pacientes criticos con ventilacion mecanica. Métodos: analisis secundario de las mediciones de GET por calorimetria indirecta en pacientes criticos. Los pacientes fueron asignados de forma 2:1 por un paquete estadistico; el primer grupo se empleo para desarrollar la nueva ecuacion predictiva del GET (grupo predictivo) y el segundo para validarla (grupo validacion). La calorimetria indirecta se realizo con tres calorimetros diferentes: la bolsa de Douglas, un computador metabolico y el equipo CalorimetR. Hemos desarrollado la nueva ecuacion predictiva del GET utilizando el GET medido (en kcal/kg/d), como variable dependiente, y como variables independientes los diferentes factores que influyen en el gasto energetico: edad, genero, indice de masa corporal (IMC) y tipo de lesion. Resultados: el grupo de prediccion incluyo 179 pacientes y el de validacion 91 pacientes. La ecuacion predictiva fue: GETEP = 33 - (3 x E) - (3 x IMC) - (1 x G). Donde: E (edad en anos): ≤ 50 = 0; > 50 = 1. IMC (kg / m2): 18,5- 24,9 = 0; 25-29,9 = 1; 30-34,9 = 2; 35-39,9 = 3. G (genero): hombre = 0; mujer = 1. El sesgo (IC del 95%) entre el GET medido y el predicho fue de -0,1 (-1,0 a 0,7) kcal/ kg/dia y los limites de acuerdo (} 2SD) fueron -8,0 a 7,8 kcal/kg/d. El GET por la ecuacion predictiva fue preciso (entre el 85% y el 115%) en el 73,6% de los pacientes. Conclusiones: La nueva ecuacion predictiva fue aceptable para predecir el GET de la mayoria de pacientes criticos con ventilacion mecanica en la practica clinica.