Long-term trends in critical care admissions in Wales*.

As national populations age, demands on critical care services are expected to increase. In many healthcare settings, longitudinal trends indicate rising numbers and proportions of patients admitted to ICU who are older; elsewhere, including some parts of the UK, a decrease has raised concerns with regard to rationing according to age. Our aim was to investigate admission trends in Wales, where critical care capacity has not risen in the last decade. We used the Secure Anonymised Information Linkage Databank to identify and characterise critical care admissions in patients aged ≥ 18 years from 1 January 2008 to 31 December 2017. We categorised 85,629 ICU admissions as youngest (18-64 years), older (65-79 years) and oldest (≥ 80 years). The oldest group accounted for 15% of admissions, the older age group 39% and the youngest group 46%. Relative to the national population, the incidence of admission rates per 10,000 population in the oldest group decreased significantly over the study period from 91.5/10,000 in 2008 to 77.5/10,000 (a relative decrease of 15%), and among the older group from 89.2/10,000 in 2008 to 75.3/10,000 in 2017 (a relative decrease of 16%). We observed significant decreases in admissions with high comorbidity (modified Charlson comorbidity index); increases in the proportion of older patients admitted who were considered 'fit' rather than frail (electronic frailty index); and decreases in admissions with a medical diagnosis. In contrast to other healthcare settings, capacity constraints and surgical imperatives appear to have contributed to a relative exclusion of older patients presenting with acute medical illness.

Reliability of frailty assessment in the critically ill: a multicentre prospective observational study.

Demand for critical care among older patients is increasing in many countries. Assessment of frailty may inform discussions and decision making, but acute illness and reliance on proxies for history-taking pose particular challenges in patients who are critically ill. Our aim was to investigate the inter-rater reliability of the Clinical Frailty Scale for assessing frailty in patients admitted to critical care. We conducted a prospective, multi-centre study comparing assessments of frailty by staff from medical, nursing and physiotherapy backgrounds. Each assessment was made independently by two assessors after review of clinical notes and interview with an individual who maintained close contact with the patient. Frailty was defined as a Clinical Frailty Scale rating > 4. We made 202 assessments in 101 patients (median (IQR [range]) age 69 (65-75 [60-80]) years, median (IQR [range]) Acute Physiology and Chronic Health Evaluation II score 19 (15-23 [7-33])). Fifty-two (51%) of the included patients were able to participate in the interview; 35 patients (35%) were considered frail. Linear weighted kappa was 0.74 (95%CI 0.67-0.80) indicating a good level of agreement between assessors. However, frailty rating differed by at least one category in 47 (47%) cases. Factors independently associated with higher frailty ratings were: female sex; higher Acute Physiology and Chronic Health Evaluation II score; higher category of pre-hospital dependence; and the assessor having a medical background. We identified a good level of agreement in frailty assessment using the Clinical Frailty Scale, supporting its use in clinical care, but identified factors independently associated with higher ratings which could indicate personal bias.

Defining sepsis on the wards: results of a multi-centre point-prevalence study comparing two sepsis definitions.

Our aim was to prospectively determine the predictive capabilities of SEPSIS-1 and SEPSIS-3 definitions in the emergency departments and general wards. Patients with National Early Warning Score (NEWS) of 3 or above and suspected or proven infection were enrolled over a 24-h period in 13 Welsh hospitals. The primary outcome measure was mortality within 30 days. Out of the 5422 patients screened, 431 fulfilled inclusion criteria and 380 (88%) were recruited. Using the SEPSIS-1 definition, 212 patients had sepsis. When using the SEPSIS-3 definitions with Sequential Organ Failure Assessment (SOFA) score ≥ 2, there were 272 septic patients, whereas with quickSOFA score ≥ 2, 50 patients were identified. For the prediction of primary outcome, SEPSIS-1 criteria had a sensitivity (95%CI) of 65% (54-75%) and specificity of 47% (41-53%); SEPSIS-3 criteria had a sensitivity of 86% (76-92%) and specificity of 32% (27-38%). SEPSIS-3 and SEPSIS-1 definitions were associated with a hazard ratio (95%CI) 2.7 (1.5-5.6) and 1.6 (1.3-2.5), respectively. Scoring system discrimination evaluated by receiver operating characteristic curves was highest for Sequential Organ Failure Assessment score (0.69 (95%CI 0.63-0.76)), followed by NEWS (0.58 (0.51-0.66)) (p < 0.001). Systemic inflammatory response syndrome criteria (0.55 (0.49-0.61)) and quickSOFA score (0.56 (0.49-0.64)) could not predict outcome. The SEPSIS-3 definition identified patients with the highest risk. Sequential Organ Failure Assessment score and NEWS were better predictors of poor outcome. The Sequential Organ Failure Assessment score appeared to be the best tool for identifying patients with high risk of death and sepsis-induced organ dysfunction.

Effect of early tracheostomy on resource utilization and clinical outcomes in critically ill patients: meta-analysis of randomized controlled trials.

BACKGROUND: Early tracheostomy may decrease the duration of mechanical ventilation, sedation exposure, and intensive care stay, possibly resulting in improved clinical outcomes, but the evidence is conflicting. METHODS: Systematic review and meta-analysis of randomized trials in patients allocated to tracheostomy within 10 days of start of mechanical ventilation was compared with placement of tracheostomy after 10 days if still required. Medline, EMBASE, the Cochrane Controlled Clinical Trials Register, and Google Scholar were searched for eligible trials. The co-primary outcomes were mortality within 60 days, and duration of mechanical ventilation, sedation, and intensive care unit stay. Secondary outcomes were the number of tracheostomy procedures performed, and incidence of ventilator-associated pneumonia (VAP). Outcomes are described as relative risk or weighted mean difference with 95% confidence intervals. RESULTS: Of note, 4482 publications were identified and 14 trials enrolling 2406 patients were included. Tracheostomy within 10 days was not associated with any difference in mortality [risk ratio (RR): 0.93 (0.83-1.05)]. There were no differences in duration of mechanical ventilation [-0.19 days (-1.13-0.75)], intensive care stay [-0.83 days (-2.05-0.40)], or incidence of VAP. However, duration of sedation was reduced in the early tracheostomy groups [-2.78 days (-3.68 to -1.88)]. More tracheostomies were performed in patients randomly assigned to receive early tracheostomy [RR: 2.53 (1.18-5.40)]. CONCLUSION: We found no evidence that early (within 10 days) tracheostomy reduced mortality, duration of mechanical ventilation, intensive care stay, or VAP. Early tracheostomy leads to more procedures and a shorter duration of sedation.

Short-term effects of N-acetylcysteine and ischemic preconditioning in a canine model of hepatic ischemia-reperfusion injury.

AIMS: We evaluated the possibility that repeated ischemic preconditioning or N-acetylcysteine (NAC) could prevent ischemia-reperfusion injury as determined by indocyanine green plasma disappearance rate (ICG-PDR) or has favorable hemodynamic effects during reperfusion in an in vivo canine liver model. METHODS: Under general anesthesia, 3 groups of mongrel dogs (n = 5 per group) were subjected to (1) 60-min hepatic ischemia, (2) same ischemia preceded by intravenous administration of 150 mg kg(-1) NAC, and (3) three episodes of IPC (10-min ischemia followed by 10-min reperfusion) prior to same ischemia. Hepatic reperfusion was maintained for a further 180 min, with hemodynamic and hepatic function parameters monitored throughout. RESULTS: Plasma disappearance rate of indocyanine green and serum levels of aspartate transferase and alanine transferase showed no significant differences between groups. Although liver injury was obvious, reflected by hemodynamic, blood gas, and liver function tests, NAC and IPC failed to prevent decay in hepatic function in this canine model. CONCLUSION: The results do not support the hypothesis that short-term use of NAC and IPC is beneficial in hepatic surgery.

In-hospital clinical outcomes after upper gastrointestinal surgery: Data from an international observational study.

AIMS: Previous research suggests that patients undergoing upper gastrointestinal surgery are at high risk of poor postoperative outcomes. The aim of our study was to describe patient outcomes after elective upper gastrointestinal surgery at a global level. METHODS: Prospective analysis of data collected during an international seven-day cohort study of 474 hospitals in 27 countries. Patients undergoing elective upper gastrointestinal surgery were recruited. Outcome measures were in-hospital complications and mortality at 30-days. Results are presented as n(%) and odds ratios with 95% confidence intervals. RESULTS: 2139 patients were included, of whom 498 (23.2%) developed one or more postoperative complications, with 30 deaths (1.4%). Patients with complications had longer median hospital stay 11 (6-18) days vs. 5 (2-10) days. Infectious complications were most frequent, affecting 368 (17.2%) patients. 328 (15.3%) patients were admitted to critical care postoperatively, of whom 161 (49.1%) developed a complication with 14 deaths (4.3%). In a multivariable logistic regression model we identified age (OR 1.02 [1.01-1.03]), American Society of Anesthesiologists physical status III (OR 2.12 [1.44-3.16]) and IV (OR 3.23 [1.72-6.09]), surgery for cancer (OR 1.63 [1.27-2.11]), open procedure (OR 1.40 [1.10-1.78]), intermediate surgery (OR 1.75 [1.12-2.81]) and major surgery (OR 2.65 [1.72-4.23]) as independent risk factors for postoperative complications. Patients undergoing major surgery for upper gastrointestinal cancer experienced twice the rate of complications compared to those undergoing other procedures (224/578 patients [38.8%] versus 274/1561 patients [17.6%]). CONCLUSIONS: Complications and death are common after upper gastrointestinal surgery. Patients undergoing major surgery for cancer are at greatest risk.

Developing a digital data collection platform to measure the prevalence of sepsis in Wales.

OBJECTIVE: To develop a secure, efficient, and easy-to-use data collection platform to measure the prevalence of sepsis in Wales over 24 hours. MATERIALS AND METHODS: Open Data Kit was used on Android devices with Google App Engine and a digital data collection form. RESULTS: A total of 184 students participated in the study using 59 devices across 16 hospitals, 1198 datasets were submitted, and 97% of participants found the Open Data Kit form easy to use. DISCUSSION: We successfully demonstrated that by combining a reliable Android device, a free open-source data collection framework, a scalable cloud-based server, and a team of 184 medical students, we can deliver a low-cost, highly reliable platform that requires little training or maintenance, providing results immediately on completion of data collection. CONCLUSION: Our platform allowed us to measure, for the first time, the prevalence of sepsis in Wales over 24 hours.

Use of cisatracurium in critical care: a review of the literature.

Cisatracurium is currently one of the most commonly used neuromuscular blocking agent (NMBA) in intensive care units. Cisatracurium was developed primarily for anaesthetic purposes in order to attempt to resolve some of the problems associated with earlier NMBAs, such as histamine release and laudanosine accumulation. Cisatracurium, the the R-cis-R-cis isomer of atracurium, is up to 5 times more potent than atracurium and so is administered in smaller quantities and produces a lesser degree of laudanosine accumulation in the plasma. In both adult and paediatric settings cisatracurium has favourable pharmacological characteristics compared to vecuronium, a steroid based NMBA often used in critical care. Recent randomised clinical trials suggested that the use of cisatracurium is associated with better outcome in acute respiratory distress syndrome (ARDS). Its use has been associated with better outcomes in therapeutic hypothermia and in traumatic brain injury. Although it has many favorable pharmacological properties, it is more expensive than comparable agents and some safety concerns persist regarding adverse events associated with the drug. The aim of the present study was to perform the first comprehensive review to date of all literature relating to the use of cisatracurium in critically ill patients.

[Inflammatory markers after surgical treatment of esophageal tumors]. / Gyulladásos markerek szintjének vizsgálata tumor miatti nyelócsómútétek után.

Oesophagectomies carry the risk of postoperative sepsis and mortality. The aim of this study was to evaluate the course of microalbuminuria, serum procalcitonin and C-reactive protein levels following oesophagectomies. Twenty one patients undergoing elective oesophagectomy were studied. Serum procalcitonin and C-reactive protein levels were determined on arrival on the intensive care unit (t0) and then daily (t24, t48, t72). Microalbuminuria (expressed as urine albumin:creatinine ratio, mg/mmol) was measured before (tpre), and after surgery (t0, t6, t24, t48, t72). For statistical analysis Wilcoxon test was used. The clinical course of the patients studied was uneventful during the first 72 hours as monitored by daily Multiple Organ Dysfunction Scores. Preoperative microalbuminuria levels were normal (< 10 mg/mmol). Levels at t0 increased significantly but then (t6-24) they returned to normal. Serum procalcitonin (normal: < 0.5 ng/ml) at t0 was slightly elevated and by t24 it increased significantly (median: 2.7 ng/ml, p < 0.05) and remained high for the rest of the study: t48-72. C-reactive protein was normal at t0 (< 10 mg/l) and by t24 it increased dramatically (up to 10-20 times to the normal value) until t48. At t72 it decreased, but still remained in the abnormal range. This study found, that the surgical insult resulted a significant increase in microalbuminuria, serum procalcitonin and C-reactive protein levels. However, the changes were not accompanied by the clinical signs of sepsis or multiple organ dysfunction in the early postoperative period following oesophagectomies.

The influence of allogenic blood transfusion in patients having free-flap primary surgery for oral and oropharyngeal squamous cell carcinoma.

The influence of perioperative blood transfusion in oral and oropharyngeal squamous cell carcinoma remains uncertain. It is believed that blood transfusion downregulates the immune system and may have an influence on cancer recurrence and survival. In all, 559 consecutive patients undergoing primary surgery for oral and oropharyngeal squamous cell carcinoma between 1992 and 2002 were included in this study. Known prognostic variables along with transfusion details were obtained from head and neck cancer and blood transfusion service databases, respectively. Adjusting for relevant prognostic factors in Cox regression, the hazard ratio for patients having 3 or more transfused units relative to those not transfused was 1.52 (95% confidence interval (CI) 0.93-2.47) for disease-specific and 1.52 (95% CI 1.05-2.22) for overall mortality. Blood transfusion of 3 or more units might confer a worse prognosis in patients undergoing primary surgery for oral and oropharyngeal squamous cell carcinoma. Therefore, every effort should be made to limit the amount of blood transfused to the minimum requirement.

Does transthoracic compared to transhiatal resection alter the early postoperative course of oesophagectomy?

SUMMARY: Several techniques for esophageal resections have been reported. However, clear clinical evidence is still lacking whether any of the procedures is superior to the others regarding morbidity and mortality in the early postoperative period. Two operative approaches for esophageal carcinoma, transhiatal and transthoracic, were compared with respect to operative morbidity, mortality and systemic inflammatory response. In our prospective study between 2000 and 2002 83 patients were investigated. In a retrospective post hoc analysis patients were divided into two groups due to the performed operational procedure, transhiatal (TH) or transthoracic (TT). Multiple Organ Dysfunction Score (MODS) was monitored daily (t1,t2,t3). Serum procalcitonin (PCT) levels were determined on admission to the ICU (t0), then 24 hourly (t24,t48,t72). Microalbuminuria (M:Cr) was measured before (tp), and after surgery (t0,t6,t24,t48,t72). For statistical analysis Wilcoxon rank sum test, Mann-Whitney U-test and chi-square test were used as appropriate. We examined 52 patients in the TH group, and 31 patients in the TT group. There was no significant difference between the two groups regarding age, male/female ratio, and SAPS II scores. Operations lasted significantly longer in the TT group: 375 (300-480) min compared to the TH group 240 375 (180-319) min, P < 0.001. ICU mortality was similar in both groups (TH: 46 survivors/6 non-survivors; TT: 27 survivors/4 non-survivors; P = 0.607, respectively). Daily MODS did not differ significantly between the two groups. The observed inflammatory markers (PCT and M:Cr) followed the pattern we described earlier, without significant difference. In this study there was no difference in the clinical and biochemical variables of the patients between the transthoracic and transhiatal groups. The observed early postoperative morbidity and mortality may indicate, that both procedures can be considered as procedures with similar postoperative risk.

Increased glomerular permeability and pulmonary dysfunction following major surgery: correlation of microalbuminuria and PaO/FiO ratio.

BACKGROUND: The aim of our trial was to evaluate the ability of microalbuminuria as an indicator of outcome and to investigate its relationship with the postoperative respiratory dysfunction in the initial postoperative period in a high-risk patient group. METHODS: In our prospective, observational study patients were consecutively recruited following elective oesophagectomy, total gastrectomy, Whipple-resection of the pancreas and liver resection due to tumour removal. Microalbuminuria (expressed as urine albumin:creatinine ratio, M:Cr) was measured before (tp), and after surgery (t0, t6, t24, t48, t72). Multiple Organ Dysfunction Scores were monitored on ICU admission than daily (t1, t2, t3). For statistical analysis, Wilcoxon's rank-sum test, Mann-Whitney's U-test, receiver operating characteristic curve analysis and Spearman's rho test were used as appropriate. RESULTS: One hundred and forty patients (118 survivors and 22 non-survivors) were recruited. Significantly higher Multiple Organ Dysfunction Scores were observed in non-survivors throughout the study period (P < 0.001). Microalbuminuria (Cr) increased significantly (P < 0.01) on admission to the ICU (t0) compared with the preoperative levels, but levels returned to normal within 6 h and remained so for the rest of the study. There was a significant difference between survivors and non-survivors at t0 (P < 0.01). However the ROC curve indicated that M:Cr is not a reliable descriptor of outcome. Comparison of Cr values with the PaO2/FiO2 ratio showed an inverse relationship on admission, which remained so for t24 and t48. CONCLUSION: M:Cr measured on admission to the ICU was significantly higher in non-survivors than in survivors, and also showed an inverse relationship with the PaO2/FiO2 ratio following extended abdominal surgery. However, on admission, M:Cr did not discriminate survivors from non-survivors. Further studies are required to evaluate the prognostic value of this test for postoperative patients with risk of respiratory failure.

Lack of effect of prophylactic N-acetylcysteine on postoperative organ dysfunction following major abdominal tumour surgery: a randomized, placebo-controlled, double-blinded clinical trial.

Sepsis and respiratory dysfunction leading to multiple system organ failure remains the leading cause of postoperative morbidity and mortality following major surgical procedures. It has been suggested the oxygen free radicals might play a pivotal role in this process. The aim of this study was to investigate whether short-term infusion of N-acetylcysteine (N-acetylcysteine), a potent antioxidant, administered before and during extensive abdominal surgery, could ameliorate the progression of early postoperative organ dysfunction and improve oxygenation. Out of the 93 patients, 47 received N-acetylcysteine and 46 were given placebo in a randomized, controlled, double-blinded fashion. Patients received N-acetylcysteine (150 mg.kg-1 bolus followed by a continuous infusion of 12 mg.kg-1.h-1) or the same volume of placebo (5% dextrose) during surgery. Treatment effect on organ function was assessed by organ dysfunction scores according to physiological parameters of six main organ systems: respiratory, cardiovascular, renal, hepatic, haematological and central nervous system. The scores were obtained on admission, then daily during the first three postoperative days. For statistical analysis Mann-Whitney U and Chi-squared tests were used. There was no significant difference between the two groups in any of the six organ dysfunction parameters, length of intensive care stay, days of mechanical ventilation and mortality. Our results do not support the routine use of N-acetylcysteine as a prophylactic measure during surgery, and reinforce previous evidence which challenges the indication of N-acetylcysteine in the critically ill.

Correlation between extravascular lung water and oxygenation in ALI/ARDS patients in septic shock: possible role in the development of atelectasis?

This study aimed to evaluate the relationship between PaO2/FiO2 ratio and extravascular lung water in septic shock-induced acute respiratory distress syndrome in a prospective observational clinical trial. Twenty-three patients suffering from sepsis induced acute respiratory distress syndrome were recruited. All patients were ventilated in pressure control/support mode. Haemodynamic parameters were determined by arterial thermodilution (PiCCO) eight hourly for 72 hours. At the same time blood gas analyses were done and respiratory parameters were also recorded. Data are presented as mean +/-SD. For statistical analysis Pearson's correlation test, and analysis of variance (ANOVA) was used respectively. Significant negative correlation was found between extravascular lung water and PaO2/FiO2 (r = -0.355, P < 0.001), and significant positive correlation was shown between extravascular lung water and PEEP (r=0.557, P<0.001). A post-hoc analysis was performed when "low" PEEP: < 10 cmH2O and "high" PEEP: (10 cmH2O PEEP was applied, and neither the oxygenation, nor the driving pressure or the PaCO2 differed significantly, but the extravascular lung water showed significant difference when "high" or "low" PEEP was applied (13+/-5 vs 9+/-2 ml/kg respectively, P=0.001). This study found significant negative correlation between extravascular lung water and PaO2/FiO2. The mechanism by which extravascular lung water affects oxygenation is unknown but the significant positive correlation between PEEP and extravascular lung water shown in this trial suggests that the latter may have a role in the development of alveolar atelectasis.