Pulmonary hypertension is not a risk factor for grade 3 primary graft dysfunction after lung transplantation.

Grade 3 primary graft dysfunction (PGD3) represents the most important risk factor for patient mortality during the first year after lung transplantation (LTX). We investigated whether pretransplant pulmonary hypertension (PH) is a risk factor for the development of PGD3. This retrospective, single-center cohort study included 96 candidates undergoing right heart catheterization (RHC) prior to being listed for LTX between March 2000 and October 2015. Based on their mean pulmonary artery pressure (mPAP) levels, the patients were classified into 3 groups: (1) <25 mm Hg, (2) 25-34 mm Hg and (3) ≥35 mm Hg. Forty-seven patients were classified in group 1, 31 in group 2, and 18 in group 3. Fifteen recipients (16%, 95%-CI 8-23) developed PGD3. In the univariate analysis, the diagnosis of interstitial lung disease (ILD) compared to COPD (OR: 7.06, P = .005), blood transfusion >1000 mL during surgery (OR: 5.25, P = .005), the need for intra-operative cardio-pulmonary bypass (CPB) or extra-corporeal membrane oxygenation (ECMO) (OR: 4, P = .027), mPAP (OR 1.06, P = .007) and serum high density lipoprotein-cholesterol (HDL-C) (OR 0.09, P = .005) were associated with PGD3. In the multivariable logistic regression analysis, only HDL-C (OR 0.10, P = .016) was associated with PGD3 based on our single-center cohort data analysis.

Effect of diagnosis related groups implementation on the intensive care unit of a Swiss tertiary hospital: a cohort study.

BACKGROUND: In 2013 the Swiss Diagnosis Related Groups ((Swiss)-DRG) was implemented in Intensive Care Units (ICU). Its impact on hospitalizations has not yet been examined. We compared the number of ICU admissions, according to clinical severity and referring institution, and screened whether implementation of Swiss-DRG affected admission policy, ICU length-of-stay (ICU-LOS) or ICU mortality. METHODS: Retrospective, single centre, cohort study conducted at the University Hospital Zurich, Switzerland between January 2009 and end of September 2013. Demographic and clinical data was retrieved from a quality assurance database. RESULTS: Admissions (n = 17,231) before the introduction of Swiss-DRG were used to model expected admissions after DRG, and then compared to the observed admissions. Forecasting matched observations in patients with a high clinical severity admitted from internal units and external hospitals (admitted / predicted: 709 / 703, [95% Confidence Interval (CI), 658-748] and 302 / 332, [95% CI, 269-365] respectively). In patients with low severity of disease, in-house admissions became more frequent than expected and external admission were less frequent (admitted / predicted: 1972 / 1910, [95% CI, 1898-1940] and 436 / 518, [95% CI, 482-554] respectively). Various mechanisms related to Swiss-DRG may have led to these changes. DRG could not be linked to significant changes in regard to ICU-LOS and ICU mortality. CONCLUSIONS: DRG introduction had not affected ICU admissions policy, except for an increase of in-house patients with a low clinical severity of disease. DRG had neither affected ICU mortality nor ICU-LOS.

Low flow veno-venous extracorporeal CO2 removal for acute hypercapnic respiratory failure.

BACKGROUND: Ventilation with low tidal volume and airway pressure results in a survival benefit in ARDS patients. Previous research suggests that avoiding mechanical ventilation altogether may be beneficial in some cases of respiratory failure. Our hypothesis was that low flow veno-venous extracorporeal CO2 removal (ECCO2R) enables maintenance of a lung protective ventilation strategy or awake spontaneous ventilation despite severe hypercapnic respiratory failure (HRF). METHODS: Twenty patients with HRF were investigated while mechanically ventilated (N.=14) or breathing spontaneously close to respiratory exhaustion (N.=6). Low flow ECCO2R was performed using a hemoperfusion device with a polypropylene gas-exchanger. RESULTS: Causes of HRF were severe ARDS (N.=11), COPD (N.=4), chronic lung transplant rejection (N.=3) and cystic fibrosis (N.=2). During the first 8h of ECCO2R, PaCO2 decreased from 10.6 (9.3-12.9) to 7.9 (7.3-9.3) kPa (P<0.001) and pH increased from 7.23 (7.09-7.40) to 7.36 (7.27-7.41) (P<0.05). Thereafter, steady state was achieved while maintaining lung protective tidal volume (4.7 (3.8-6.5) mL/kg) and peak ventilator pressure (28 (27-30) mbar at 24 h). During the first 48 h, thrombocyte count decreased by 52% (P<0.01), Fibrinogen by 38% (P<0.05). Intubation could be avoided in all spontaneously breathing patients. In 4/6 high blood flow extracorporeal circulation was required due to increased oxygen demand. 6/14 mechanically ventilated patients recovered from respiratory support. CONCLUSIONS: Our results suggest that in mechanically ventilated patients with HRF, low flow ECCO2R supports the maintenance of lung protective tidal volume and peak ventilator pressure. In selected awake patients with acute HRF, it may be a novel treatment approach to avoid mechanical ventilation, hence preventing ventilator- and sedation-associated morbidity and mortality.

Pretransplant dyslipidaemia influences primary graft dysfunction after lung transplantation.

OBJECTIVES: Primary graft dysfunction (PGD) is a major cause of mortality within the first year following lung transplantation. Pulmonary hypertension, elevated body mass index (BMI), prolonged ischaemic time of the graft, intraoperative blood transfusions >1000 ml and the use of cardiopulmonary bypass or extracorporeal membrane oxygenation increase the risk for PGD. We aimed to evaluate whether dyslipidaemia is an additional risk factor for the development of PGD. METHODS: We retrospectively analysed demographic and clinical data of 264 patients who received their first bilateral lung transplantation between March 2000 and October 2013 at our institution. The endpoint was PGD grade 3 at any time, defined according to the International Society for Heart and Lung Transplantation (ISHLT) criteria. Fasting lipid profiles at listing time or just before transplantation (baseline) were documented and dyslipidaemia was defined as any of the parameters being out of range. Comparisons of continuous variables between patients with PGD grade 3 and patients without were performed with the Mann-Whitney U-test, whereas proportions were compared with the χ(2) test. Continuous variables were presented as arithmetic means with standard deviation for ease of comparison, but levels of statistical significance were computed using the appropriate non-parametric statistical test. To identify PGD risk factors, a forward stepwise logistic regression model was used. RESULTS: PGD occurred in 63 recipients (24%). Pretransplant dyslipidaemia was documented in 153 recipients (58%) and was significantly more prevalent among recipients developing PGD (45 vs 108, P < 0.013). Despite various underlying pulmonary pathologies, higher triglyceride (TG) levels (1.41 ± 0.78 vs 1.16 ± 0.78, P < 0.012), lower high-density lipoprotein-cholesterol (HDL-C) concentrations (1.24 ± 0.55 vs 1.57 ± 0.71, P < 0.0005) and higher cholesterol/HDL-C values (3.80 ± 2.02 vs 3.00 ± 0.92, P < 0.0005) were associated with a lower incidence of PGD. Patients with PGD had significantly longer ischaemic time (350 ± 89 vs 322 ± 91, P = 0.017) and higher BMI (23 ± 5 vs 21 ± 4.4, P < 0.007). CONCLUSIONS: Dyslipidaemia seems to be an independent risk factor for PGD after lung transplantation: low circulating levels of HDL-C and hypertriglyceridaemia increase the incidence of PGD. Even if HDL-C levels are difficult to alter today, triglyceride and cholesterol levels can be addressed therapeutically and may have a positive influence on the development of PGD.

Extracorporeal membrane oxygenation: beneficial strategy for lung transplant recipients.

The role of extracorporeal membrane oxygenation (ECMO) as a therapeutic strategy has been very well documented for over a decade now with consistently positive remarks. The aim of the present study was analyzing the outcome of ECMO application in our lung transplant program, especially the feasibility and safety of our ECMO approach. Therefore, we retrospectively analyzed the data of 15 patients recipients requiring ECMO support. We analyzed clinical data, complications, and survival of the lung-transplanted population that needed ECMO support at our institution from 2006-2009. During that period, 19 applications of ECMO were done on 15 adult patients with the following indications: primary graft dysfunction (10 patients), "bridge to transplantation" (five), pulmonary hypertension (three), and severe acute respiratory distress syndrome (one). At 28 days, the overall survival was 93% (14 of 15 patients) and 12 of these patients (80%) survived at least 6 months. Complications included acute renal insufficiency with temporary need of renal replacement therapy (53%), bleeding (33%), critical illness polyneuropathy (66%), and reversible thrombocytopenia (73%). Based on the evaluation of the patients in this analysis, ECMO seems to be a safe therapeutic approach in lung transplant recipients with severe respiratory failure directly after transplantation.

Pretransplant dyslipidaemia determines outcome in lung transplant recipients.

BACKGROUND: There is little knowledge about the effect of dyslipidaemia on the outcome after lung transplantation. Thus, the aim of this retrospective single centre study was to analyse the impact of the plasma lipid profile on mortality in lung transplant recipients. From January 2000 to December 2008 the charts of 172 consecutive lung transplantation recipients were analysed. At baseline and after one year lipid profiles were routinely collected. During the follow-up major cardiovascular events (MCE; beginning of dialysis, cerebrovascular insult or myocardial infarction) were recorded. The follow-up period ended December 2010. FINDINGS: Over all total cholesterol (4.3 ± 1.6 vs. 5.4 ± 1.3 mmol/l, p < 0.0001), triglycerides (1.2 ± 0.7 vs. 2.4 ± 1.3 mmol/l, p < 0.0001), HDL (1.5 ± 0.6 vs. 1.7 ± 0.6 mmol/l, p = 0.003) and TC/HDL ratio (3.0 ± 1.0 vs. 3.6 ± 1.2, p = 0.002) increased significantly after 1 year.During the observational period 6.9% (10 patients) suffered a major cardiac event. In univariate analysis MCE was associated with baseline TC: on average the event-group had a 33% higher baseline TC (5.6 vs. 4.2 mmol/l, OR 1.6, CI 1.1 - 2.2, p = 0.02). The total mortality in the observational period was 25% (36 patients overall). In univariate analysis mortality was associated with increased TC/HDL ratio. The non-survivors had on average a 22% higher baseline TC/HDL ratio (3.6 vs. 2.8, HR 2.8, CI 1.2 - 3.5, p = 0.001). There was no association between mortality and TC (p = 0.33), triglycerides (p = 0.34), HDL (p = 0.78) and creatinine (p = 0.73). In a multivariate model the hazard ratio was 1.5 (1.2 - 1.9, p = 0.001) per increase of 0.4 TC/HDL ratio. CONCLUSIONS: This study shows that the total cholesterol before transplantation is associated with the incidence of MCE and the cholesterol/HDL ratio with mortality in lung transplanted recipients.

The relationship between preoperative creatinine clearance and outcomes for patients undergoing liver transplantation: a retrospective observational study.

BACKGROUND: Renal failure with following continuous renal replacement therapy is a major clinical problem in liver transplant recipients, with reported incidences of 3% to 20%. Little is known about the significance of postoperative acute renal failure or acute-on-chronic renal failure to postoperative outcome in liver transplant recipients. METHODS: In this post hoc analysis we compared the mortality rates of 135 consecutive liver transplant recipients over 6 years in our center subject to their renal baseline conditions and postoperative RRT. We classified the patients into 4 groups, according to their preoperative calculated Cockcroft formula and the incidence of postoperative renal replacement therapy. Data then were analyzed in regard to mortality rates and in addition to pre- and peritransplant risk factors. RESULTS: There was a significant difference in ICU mortality (p=.008), hospital mortality (p=.002) and cumulative survival (p<.0001) between the groups. The highest mortality rate occurred in the group with RRT and normal baseline kidney function (20% ICU mortality, 26.6% hospital mortality and 50% cumulative 1-year mortality, respectively). The hazard ratio in this group was 9.6 (CI 3.2-28.6, p=.0001). CONCLUSION: This study shows that in liver transplant recipient's acute renal failure with postoperative RRT is associated with mortality and the mortality rate is higher than in patients with acute-on-chronic renal failure and postoperative renal replacement therapy.

Association of intraoperative transfusion of blood products with mortality in lung transplant recipients.

BACKGROUND: The impact of intraoperative transfusion on postoperative mortality in lung transplant recipients is still elusive. METHODS: Univariate and multivariate analysis were performed to investigate the influence of red blood cells (RBCs) and fresh frozen plasma (FFP) on mortality in 134 consecutive lung transplants recipients from September 2003 until December 2008. RESULTS: Intraoperative transfusion of RBCs and FFP was associated with a significant increase in mortality with odds ratios (ORs) of 1.10 (1.03 to 1.16, P = 0.02) and 1.09 (1.02 to 1.15, P = 0.03), respectively. For more than four intraoperatively transfused RBCs multivariate analysis showed a hazard ratio for mortality of 3.8 (1.40 to 10.31, P = 0.003). Furthermore, non-survivors showed a significant increase in renal replacement therapy (RRT) (36.6% versus 6.9%, P <0.0001), primary graft dysfunction (PGD) (39.3% versus 5.9%, P <0.0001), postoperative need of extracorporeal membrane oxygenation (ECMO) (26.9% versus 3.1%, P = 0.0019), sepsis (24.2% versus 4.0%, P = 0.0004), multiple organ dysfunction syndrome (MODS) (26.9% versus 3.1%, P <0.0001), infections (18.1% versus 0.9%, P = 0.0004), retransplantation (12.1% versus 6.9%, P = 0.039) and readmission to the ICU (33.3% versus 12.8%, P = 0.024). CONCLUSIONS: Intraoperative transfusion is associated with a strong negative influence on outcome in lung transplant recipients.

Two different hematocrit detection methods: different methods, different results?

BACKGROUND: Less is known about the influence of hematocrit detection methodology on transfusion triggers. Therefore, the aim of the present study was to compare two different hematocrit-assessing methods. In a total of 50 critically ill patients hematocrit was analyzed using (1) blood gas analyzer (ABLflex 800) and (2) the central laboratory method (ADVIA® 2120) and compared. FINDINGS: Bland-Altman analysis for repeated measurements showed a good correlation with a bias of +1.39% and 2 SD of +/- 3.12%. The 24%-hematocrit-group showed a correlation of r2 = 0.87. With a kappa of 0.56, 22.7% of the cases would have been transfused differently. In the-28%-hematocrit group with a similar correlation (r2 = 0.8) and a kappa of 0.58, 21% of the cases would have been transfused differently. CONCLUSIONS: Despite a good agreement between the two methods used to determine hematocrit in clinical routine, the calculated difference of 1.4% might substantially influence transfusion triggers depending on the employed method.

Increasing hematocrit above 28% during early resuscitative phase is not associated with decreased mortality following severe traumatic brain injury.

BACKGROUND: To prevent iatrogenic damage, transfusions of red blood cells should be avoided. For this, specific and reliable transfusion triggers must be defined. To date, the optimal hematocrit during the initial operating room (OR) phase is still unclear in patients with severe traumatic brain injury (TBI). We hypothesized that hematocrit values exceeding 28%, the local hematocrit target reached by the end of the initial OR phase, resulted in more complications, increased mortality, and impaired recovery compared to patients in whom hematocrit levels did not exceed 28%. METHODS: Impact of hematocrit (independent variable) reached by the end of the OR phase on mortality and morbidity determined by the extended Glasgow outcome scale (eGOS; dependent variables) was investigated retrospectively in 139 TBI patients. In addition, multiple logistic regression analysis was performed to identify additional important variables. FINDINGS: Following severe TBI, mortality and morbidity were neither aggravated by hematocrit above 28% reached by the end of the OR phase nor worsened by the required transfusions. Upon multiple logistic regression analysis, eGOS was significantly influenced by the highest intracranial pressure and the lowest cerebral perfusion pressure values during the initial OR phase. CONCLUSIONS: Based on this retrospective observational analysis, increasing hematocrit above 28% during the initial OR phase following severe TBI was not associated with improved or worsened outcome. This questions the need for aggressive transfusion management. Prospective analysis is required to determine the lowest acceptable hematocrit value during the OR phase which neither increases mortality nor impairs recovery. For this, a larger caseload and early monitoring of cerebral metabolism and oxygenation are indispensable.

Noninvasive cardiac output and blood pressure monitoring cannot replace an invasive monitoring system in critically ill patients.

BACKGROUND: Monitoring of cardiac output and blood pressure are standard procedures in critical care medicine. Traditionally, invasive techniques like pulmonary artery catheter (PAC) and arterial catheters are widely used. Invasiveness bears many risks of deleterious complications. Therefore, a noninvasive reliable cardiac output (CO) and blood pressure monitoring system could improve the safety of cardiac monitoring. The aim of the present study was to compare a noninvasive versus a standard invasive cardiovascular monitoring system. METHODS: Nexfin HD is a continuous noninvasive blood pressure and cardiac output monitor system and is based on the development of the pulsatile unloading of the finger arterial walls using an inflatable finger cuff. During continuous BP measurement CO is calculated. We included 10 patients with standard invasive cardiac monitoring system (pulmonary artery catheter and arterial catheter) comparing invasively obtained data to the data collected noninvasively using the Nexfin HD. RESULTS: Correlation between mean arterial pressure measured with the standard arterial monitoring system and the Nexfin HD was r2 = 0.67 with a bias of -2 mmHg and two standard deviations of +/- 16 mmHg. Correlation between CO derived from PAC and the Nexfin HD was r2 = 0.83 with a bias of 0.23 l/min and two standard deviations of +/- 2.1 l/min; the percentage error was 29%. CONCLUSION: Although the noninvasive CO measurement appears promising, the noninvasive blood pressure assessment is clearly less reliable than the invasively measured blood pressure. Therefore, according to the present data application of the Nexfin HD monitoring system in the ICU cannot be recommended generally. Whether such a tool might be reliable in certain critically ill patients remains to be determined.

Differential influence of arterial blood glucose on cerebral metabolism following severe traumatic brain injury.

INTRODUCTION: Maintaining arterial blood glucose within tight limits is beneficial in critically ill patients. Upper and lower limits of detrimental blood glucose levels must be determined. METHODS: In 69 patients with severe traumatic brain injury (TBI), cerebral metabolism was monitored by assessing changes in arterial and jugular venous blood at normocarbia (partial arterial pressure of carbon dioxide (paCO2) 4.4 to 5.6 kPa), normoxia (partial arterial pressure of oxygen (paO2) 9 to 20 kPa), stable haematocrit (27 to 36%), brain temperature 35 to 38 degrees C, and cerebral perfusion pressure (CPP) 70 to 90 mmHg. This resulted in a total of 43,896 values for glucose uptake, lactate release, oxygen extraction ratio (OER), carbon dioxide (CO2) and bicarbonate (HCO3) production, jugular venous oxygen saturation (SjvO2), oxygen-glucose index (OGI), lactate-glucose index (LGI) and lactate-oxygen index (LOI). Arterial blood glucose concentration-dependent influence was determined retrospectively by assessing changes in these parameters within pre-defined blood glucose clusters, ranging from less than 4 to more than 9 mmol/l. RESULTS: Arterial blood glucose significantly influenced signs of cerebral metabolism reflected by increased cerebral glucose uptake, decreased cerebral lactate production, reduced oxygen consumption, negative LGI and decreased cerebral CO2/HCO3 production at arterial blood glucose levels above 6 to 7 mmol/l compared with lower arterial blood glucose concentrations. At blood glucose levels more than 8 mmol/l signs of increased anaerobic glycolysis (OGI less than 6) supervened. CONCLUSIONS: Maintaining arterial blood glucose levels between 6 and 8 mmol/l appears superior compared with lower and higher blood glucose concentrations in terms of stabilised cerebral metabolism. It appears that arterial blood glucose values below 6 and above 8 mmol/l should be avoided. Prospective analysis is required to determine the optimal arterial blood glucose target in patients suffering from severe TBI.

Risk factors for reperfusion injury after lung transplantation.

OBJECTIVE: To assess the influence of recipient's and donor's factors as well as surgical events on the occurrence of reperfusion injury after lung transplantation. DESIGN AND SETTING: Retrospective study in the surgical intensive care unit (ICU) of a university hospital. METHODS: We collected data on 60 lung transplantation donor/recipient pairs from June 1993 to May 2001, and compared the demographic, peri- and postoperative variables of patients who experienced reperfusion injury (35%) and those who did not. RESULTS: The occurrence of high systolic pulmonary pressure immediately after transplantation and/or its persistence during the first 48 h after surgery was associated with reperfusion injury, independently of preoperative values. Reperfusion injury was associated with difficult hemostasis during transplantation (p=0.03). Patients with reperfusion injury were more likely to require the administration of catecholamine during the first 48 h after surgery (p=0.014). The extubation was delayed (p=0.03) and the relative odds of ICU mortality were significantly greater (OR 4.8, 95% CI: 1.06, 21.8) in patients with reperfusion injury. Our analysis confirmed that preexisting pulmonary hypertension increased the incidence of reperfusion injury (p<0.01). CONCLUSIONS: Difficulties in perioperative hemostasis were associated with reperfusion injury. Occurrence of reperfusion injury was associated with postoperative systolic pulmonary hypertension, longer mechanical ventilation and higher mortality. Whether early recognition and treatment of pulmonary hypertension during transplantation can prevent the occurrence of reperfusion injury needs to be investigated.