Effects of arterial load variations on dynamic arterial elastance: an experimental study.

BACKGROUND.: Dynamic arterial elastance (Ea dyn ), the relationship between pulse pressure variation (PPV) and stroke volume variation (SVV), has been suggested as a functional assessment of arterial load. The aim of this study was to evaluate the impact of arterial load changes during acute pharmacological changes, fluid administration, and haemorrhage on Ea dyn . METHODS.: Eighteen anaesthetized, mechanically ventilated New Zealand rabbits were studied. Arterial load changes were induced by phenylephrine ( n =9) or nitroprusside ( n =9). Thereafter, animals received a fluid bolus (10 ml kg -1 ), followed by stepwise bleeding (blood loss: 15 ml kg -1 ). The influence of arterial load and cardiac variables on PPV, SVV, and Ea dyn was analysed using a linear mixed-effects model analysis. RESULTS.: After phenylephrine infusion, mean ( sd ) Ea dyn decreased from 0.89 (0.14) to 0.49 (0.12), P <0.001; whereas after administration of nitroprusside, Ea dyn increased from 0.80 (0.23) to 1.28 (0.21), P <0.0001. Overall, the fluid bolus decreased Ea dyn [from 0.89 (0.44) to 0.73 (0.35); P <0.01], and haemorrhage increased it [from 0.78 (0.23) to 0.95 (0.26), P =0.03]. Both PPV and SVV were associated with similar arterial factors (effective arterial elastance, arterial compliance, and resistance) and heart rate. Furthermore, PPV was also related to the acceleration and peak velocity of aortic blood flow. Both arterial and cardiac factors contributed to the evolution of Ea dyn throughout the experiment. CONCLUSIONS.: Acute modifications of arterial load induced significant changes on Ea dyn ; vasodilatation increased Ea dyn , whereas vasoconstriction decreased it. The Ea dyn was associated with both arterial load and cardiac factors, suggesting that Ea dyn should be more properly considered as a ventriculo-arterial coupling index.

Cardiac complications associated with goal-directed therapy in high-risk surgical patients: a meta-analysis.

Patients with limited cardiopulmonary reserve are at risk of mortality and morbidity after major surgery. Augmentation of oxygen delivery index (DO2I) with i.v. fluids and inotropes (goal-directed therapy, GDT) has been shown to reduce postoperative mortality and morbidity in high-risk patients. Concerns regarding cardiac complications associated with fluid challenges and inotropes may prevent clinicians from performing GDT in patients who need it most. We hypothesized that GDT is not associated with an increased risk of cardiac complications in high-risk, non-cardiac surgical patients. We performed a systematic search of Medline, Embase, and CENTRAL databases for randomized controlled trials (RCTs) of GDT in high-risk surgical patients. Studies including cardiac surgery, trauma, and paediatric surgery were excluded. We reviewed the rates of all cardiac complications, arrhythmias, myocardial ischaemia, and acute pulmonary oedema. Meta-analyses were performed using RevMan software. Data are presented as odds ratios (ORs), [95% confidence intervals (CIs)], and P-values. Twenty-two RCTs including 2129 patients reported cardiac complications. GDT was associated with a reduction in total cardiovascular (CVS) complications [OR=0.54, (0.38-0.76), P=0.0005] and arrhythmias [OR=0.54, (0.35-0.85), P=0.007]. GDT was not associated with an increase in acute pulmonary oedema [OR=0.69, (0.43-1.10), P=0.12] or myocardial ischaemia [OR=0.70, (0.38-1.28), P=0.25]. Subgroup analysis revealed the benefit is most pronounced in patients receiving fluid and inotrope therapy to achieve a supranormal DO2I, with the use of minimally invasive cardiac output monitors. Treatment of high-risk surgical patients GDT is not associated with an increased risk of cardiac complications; GDT with fluids and inotropes to optimize DO2I during early GDT reduces postoperative CVS complications.

Raised serum cardiac troponin I concentrations predict hospital mortality in intensive care unit patients.

BACKGROUND: Recent work suggests that increased plasma concentrations of cardiac troponin I (cTnI) are common in critically ill patients and are associated with poor outcome. We measured the frequency of increased plasma cTnI concentrations during patients' stay in a mixed medical/surgical intensive care unit (ICU) and compared our findings with hospital mortality. METHODS: Basic details, organ support, and hospital mortality were recorded for all patients treated in ICU during a 6 month period. cTnI concentrations were sampled daily for all patients, using 0.04 µg litre(-1) as the upper limit of normal, and 0.12 µg litre(-1) as an additional stratification point. RESULTS: Of 663 patients, 54% were male, with a mean (sd) age of 60 (18) yr, 65% were surgical patients, and the median Acute Physiology and Chronic Ill Health II (APACHE II) score was 15 (inter-quartile range 12-20). Increased cTnI concentrations were found in 345 patients (52%) while in ICU. One hundred and twenty patients (18%) died in hospital. cTnI concentration >0.04 µg litre(-1) was associated with reduced odds of hospital survival, independent of age, medical admission, unplanned admission, APACHE II score, mechanical ventilation, and haemofiltration (adjusted odds ratio 0.25, 95% confidence interval 0.08-0.75, P=0.014). Stratification by the degree of cTnI increase revealed an incremental trend towards a lower odds of hospital survival, including for patients with 'minor' elevations of cTnI (0.05-0.12 µg litre(-1)). CONCLUSIONS: Increased serum cTnI concentrations during ICU stay independently predicts hospital mortality, even when the threshold is low. We found a trend towards an association between 'minor' elevations in cTnI and higher in-hospital mortality.

C-reactive protein as a predictor of outcome after discharge from the intensive care: a prospective observational study.

BACKGROUND: Recent studies have found plasma C-reactive protein (CRP) to be a predictor of outcome after discharge from the intensive care unit (ICU). To assess the generalizability of this finding, we assessed the value of CRP on the day of ICU discharge as a predictor of unplanned ICU readmission and unexpected death within 2 weeks. Plasma albumin and white cell count at discharge were also considered as markers associated with ongoing inflammation. METHODS: This was a single-centre observational study involving a medical-surgical ICU in a university teaching hospital. Data were prospectively collected from 1487 admissions involving 1401 patients over a 12 month period. Patients' admission details and APACHE II score were collected in addition to plasma CRP, white cell count, and albumin values from the day of discharge from ICU. We assessed the difference in these variables between patients who were readmitted, who died unexpectedly, and those who did not. RESULTS: We found that 9.9% of patients discharged were either readmitted (7.0%) or died unexpectedly (2.9%). Patients who were readmitted had a lower plasma albumin concentration [20 (16, 24) vs 22 (19, 27), P<0.001] and a higher admission APACHE II score [median (inter-quartile range, IQR) 16.5 (13, 21) vs 15 (12, 18), P=0.02]. Patients who died unexpectedly on the ward were older [mean (sd): 76 (12) vs 59 (19), P<0.001] and had a higher APACHE II score [21 (17.25, 26) vs 15 (12, 18), P<0.001]. There was not a statistically significant difference in CRP concentration between patients who either required ICU readmissions or died unexpectedly on the ward and those who did not. CONCLUSIONS: In a mixed medical-surgical intensive care, plasma CRP measured at the day of discharge from intensive care is not a predictor of readmissions or deaths.

Changes in cardiac output during air ambulance repatriation.

OBJECTIVES: To measure, with the use of suprasternal Doppler ultrasound, the hemodynamic changes in patients and volunteers during air ambulance repatriation. DESIGN: Unblinded prospective observational study. SETTING: Chartered air ambulances for the international repatriation of patients. PATIENTS AND PARTICIPANTS: Six medical crew members and seven patients transported back to hospitals in the UK. INTERVENTIONS: The measurement of non-invasive blood pressure, ECG, heart rate, oxygen saturation and hemodynamic variables with suprasternal Doppler. MEASUREMENTS AND RESULTS: There was a drop in systolic and mean arterial blood pressure in the patient's group once in the air. Oxygen saturation dropped in both groups once at cruising altitude. Heart rate remained unchanged. Stroke distance and minute distance increased significantly in the patient's group and non-significantly in the volunteers. Peak velocity increased significantly in the patient's group. There was an overall reduction of systemic vascular resistance during take off and once at cruising altitude. CONCLUSIONS: Hemodynamic changes happen during air ambulance transportation in fit and healthy volunteers and patients alike. These may be due to a combination of hypobaric hypoxia and gravitational forces. It is necessary to establish if these changes have short- or long-term effects in the critically ill.

A cost analysis of a treatment policy of a deliberate perioperative increase in oxygen delivery in high risk surgical patients.

OBJECTIVE: To investigate the cost implications of a treatment policy of a deliberate perioperative increase of oxygen delivery in high risk surgical patients. DESIGN: A cost-effectiveness analysis comparing 'protocol' high risk surgical patients in whom oxygen delivery was specifically targeted towards 600 ml/min/m2 with 'control' patients. INTERVENTIONS: In a randomised, controlled clinical trial we previously demonstrated a significant reduction in mortality (5.7% vs 22.2%, p = 0.015) and morbidity (0.68 +/- 0.16 complications vs 1.35 +/- 0.20, p = 0.008) in 'protocol' high risk surgical patients in whom oxygen delivery was specifically targeted towards 600 ml/min per m2 compared with 'control' patients. This current study retrospectively analysed the medical care and National Health Service resource use of each patient in the trial. Departmental purchasing records and business managers were consulted to identify the unit cost of these resources, and thereby the cost of treating each patient was calculated. RESULTS: The median cost of treating a protocol patient was lower than for a control patient (6,525 pounds vs 7,784 pounds) and this reduction was due mainly to a decrease in the cost of treating postoperative complications (median 213 pounds vs 668 pounds). The cost of obtaining a survivor was 31% lower in the protocol group. CONCLUSION: Perioperative increase of oxygen delivery in high risk surgical patients not only improves survival, but also provides an actual and relative cost saving. This may have important implications for the management of these patients and the funding of intensive care.

Base excess and lactate as prognostic indicators for patients admitted to intensive care.

OBJECTIVE: To examine whether values of arterial base excess or lactate taken on admission to a general intensive care unit indicate prognosis, and whether this can be used as a screening tool for future intensive care admissions. DESIGN: Observational study. SETTING: University teaching hospital general adult intensive care unit. PATIENTS: 148 consecutive patients admitted to the intensive care unit. INTERVENTIONS: Arterial blood samples were obtained on admission to the intensive care unit and 24 h following admission. MEASUREMENTS AND RESULTS: Arterial base excess and lactate concentrations were measured from the blood samples. Both base excess and arterial lactate samples on admission have good prognostic abilities (area under the curve on receiver operator characteristic analysis of 0.73, 0.78, respectively). The value of base excess on admission with the best predictive ability was a base excess more negative than -4 mmol/l, and the corresponding value for lactate was greater than 1.5 mmol/l. The combination of these two markers on admission to the intensive care unit led to a sensitivity of 80.3 % and a specificity of 58.7 % for mortality. The achievement of this combination was associated with an increased mortality (50.6 % vs. 15 %, p < 0.0001), older age (70 vs. 61.5 years, p < 0.05), a greater requirement for inotropic support (30.9 % vs. 4.5%, p < 0.0001) and higher organ failure scores both on admission and for the subsequent 24 h. CONCLUSIONS: Both base excess and lactate, or the combination of the two, can be used to predict outcome in patients admitted to the intensive care unit. These variables could be utilized to identify patients who have a high risk for mortality and thus who should be admitted to the intensive care unit.

The strong ion gap does not have prognostic value in critically ill patients in a mixed medical/surgical adult ICU.

OBJECTIVE: To examine whether the strong ion gap (SIG) or standard base excess corrected for abnormalities of serum chloride and albumin (BE(UA)) can predict outcome and to compare the prognostic abilities of these variables with standard base excess (SBE), anion gap (AG), pH, and lactate, the more traditional markers of acid-base disturbance. DESIGN: Prospective, observational study. SETTING: University teaching hospital, general adult ICU. PATIENTS: One hundred consecutive patients on admission to the ICU. MEASUREMENTS AND RESULTS: The anion gap (AG) was calculated and corrected for abnormal serum albumin (AG(corrected)). Serum lactate was measured and SBE, BE(UA), SIG, and APACHE II scores calculated for each patient. 28-day survival was recorded. There was a significant difference between the mean APACHE II (P < 0.001), SBE (P < 0.001), lactate (P = 0.008), AG (P = 0.007), pH (P < 0.001), and BE(UA) (P = 0.009) of survivors and non-survivors. There was no significant difference between the mean SIG (P = 0.088), SIDeff (P = 0.025), and SID app (P = 0.254) between survivors and non-survivors. The pH and SBE demonstrated the best ability of the acid-base variables to predict outcome (AUROC curves 0.72 and 0.71, respectively). Neither of these were as good as the APACHE II score (AUROC 0.76) CONCLUSION: Traditional indices of SBE, BE(UA,) lactate, pH, AG, and APACHE II all discriminated well between survivors and non-survivors. In this group of patients the SIG, SIDeff, and SIGapp appear to offer no advantage in prediction of outcome and their use as prognostic markers can therefore not be advocated.

A phase III, multicenter, open-label, randomized, comparative study evaluating the effect of sevoflurane versus isoflurane on the maintenance of anesthesia in adult ASA class I, II, and III inpatients.

STUDY OBJECTIVE: To compare the clinical efficacy and safety of sevoflurane and isoflurane when used for the maintenance of anesthesia in adult ASA I, II, and III inpatients undergoing surgical procedures of at least 1 hour's duration. DESIGN: Phase III, randomized, open-label clinical trial. SETTING: 12 international surgical units. PATIENTS: 555 consenting inpatients undergoing surgeries of intermediate duration. INTERVENTIONS: Subjects received either sevoflurane (n = 272) or isoflurane (n = 283) as their primary anesthetic drug, each administered in nitrous oxide (N2O) (up to 70%) and oxygen (O2) after an intravenous induction using thiopental and low-dose fentanyl. The concentration of volatile drug was kept relatively constant but some titration in response to clinical variable was permitted. Comparison of efficacy was based on observations made of the rapidly and ease of recovery from anesthesia and the frequency of untoward effects for the duration of anesthesia in the return of orientation. Safety was evaluated by monitoring adverse experiences, hematologic and non-laboratory testing, and physical assessments. In 25% of patients (all patients 171 both treatment groups at selected investigational sites), plasma inorganic fluoride concentrations were determined preoperatively, every 2 hours during maintenance, at the end of anesthesia, and at 1, 2, 4, 8, 12, 24, 48, and 72 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Emergence, response to commands, orientation, and the first request for postoperative analgesia were all more rapid following discontinuation of sevoflurane than following discontinuation of isoflurane (sevoflurane, 11.0 +/- 0.6, 12.8 +/- 0.7, 17.2 +/- 0.9, 46.1 +/- 3.0 minutes, respectively, versus isoflurane, 16.4 +/- 0.6, 18.4 +/- 0.7, 24.7 +/- 0.9, 55.4 +/- 3.2 minutes). The incidence of adverse experiences was similar for sevoflurane and isoflurane patients. Forty-eight percent of patients on the sevoflurane group had no untoward effect versus 39% in the isoflurane group. Three patients who received sevoflurane had serum inorganic fluoride levels 50 microM/I. or greater though standard tests indicated no evidence of associated renal dysfunction. CONCLUSION: Sevoflurane anesthesia, as compared with isoflurane, may be advantageous in providing a smoother clinical course with a more rapid recover.

Efficacy of functional hemodynamic parameters in predicting fluid responsiveness with pulse power analysis in surgical patients.

BACKGROUND: In this study we quantify the ability of dynamic cardiovascular parameters measured by the PulseCO™ algorithm of the LiDCO™plus monitor to predict the response to a fluid challenge in post-operative patients. METHODS: Surgical patients, admitted to the Intensive Care Unit from the operating theatre were monitored with the LiDCO™plus system. A number of static and dynamic cardiovascular measurements were recorded before and after a fluid challenge. Receiver Operator Characteristic (ROC) curve analysis was used to identify the baseline values, with optimum sensitivity and specificity, to predict responsiveness to a fluid challenge. RESULTS: Thirty-one patients were enrolled, and received protocol-based fluid challenges. Twelve (38%) responded by demonstrating an increase in stroke volume of >15%. Heart rate (HR) and central venous pressure (CVP) were not statistically different between responders and non-responders. Mean arterial pressure (mAP), systolic pressure variation (SPV), pulse pressure variation (PPV) and stroke volume variation (SVV) were statistically different between responders and non-responders. Parameters with a ROC area under the curve (AUC) significantly >0.5 included SPV 0.70 (0.52-0.88) P=0.046, PPV 0.87 (0.76-0.99) P<0.0002 and SVV 0.84 (0.71-0.96) P=0.0005. The best cut-off values (sensitivity and specificity) to predict fluid were SPV >9 mmHg (73%, 76%), PPV >13% (83%, 74%) and SVV >12.5% (75%, 83%). ROC analysis did not show the AUC to be significantly >0.5 for HR, mAP and CVP CONCLUSION: Dynamic indices measured by PulseCO™ (LiDCO) have a high sensitivity and specificity in predicting fluid responsiveness in sedated and mechanically ventilated patients. A cut-off value for PPV of 13% is the most sensitive and specific indicator of fluid responsiveness.

Patient safety in anesthesia.

Medical mistakes have been identified as resulting from a breakdown in one or more of five major areas: equipment performance, communication, staffing levels, complex environments and workloads. Because many of these areas relate directly to the practice of anesthesiology, they can contribute significantly to the safety and quality of the use of anesthesia. The specialty of anesthesia has embraced a culture of safety, resulting in many beneficial improvements for patients. The avoidance of error has led to improved outcomes, with a decrease in directly attributable rates of morbidity and mortality. Despite these improved rates, there are still areas that can be improved. This paper describes the background of these issues, discusses areas where performance has improved and identifies the areas in which there is room for further improvement.

A prospective study of the accuracy and precision of continuous cardiac output monitoring devices as compared to intermittent thermodilution.

BACKGROUND: Pulse pressure (PP) analysis from a radial arterial line is available with the LiDCO plus monitor (LiDCO, Cambridge, UK) and FloTrac/Vigileo (Edwards Lifesciences, Irvine, CA, USA). The aim of this study was to investigate the agreement of continuous PP analysis against intermittent thermodilution (ITD) using the pulmonary artery catheter (PAC). METHODS: This was a six-hour study in 29 patients monitored with a PAC. All measurements were referenced against CO measured from the average of four ITD curves from the PAC. The LiDCO plus was calibrated with a lithium dilution (PulseCOLi) and with ITD (PulseCOITD) at baseline. Measurements from Vigileo software 1.03 (APCO), LiDCO plus (PulseCOLi and PulseCOITD), CCO and ITD were taken every hour for the next six hours. The bias and precision between the two devices were calculated as well as the percentage error (PE) of agreement between the tested device and the reference. The coefficient of variation (CV) of the tested device was then derived. RESULTS: The average bias, PE and coefficient of variation for CCO vs. ITD of the tested device were 0.3 L/min, 28% and 13%, respectively; for APCO vs. ITD the calculations were -1.1 L/min, 55% and 27%; for PulseCOLi Cardiac output Blood pressure Thermodilution. ITD they were 0.5 L/min, 40% and 19%; and for PulseCOITD vs. ITD they were 0.2 L/min, -31% and 15%. CONCLUSION: APCO (Vigileo software 1.03) and PulseCOLi showed a moderate agreement with the PAC. When PulseCO was calibrated with ITD (PulseCOITD) it showed excellent agreement, demonstrating that PulseCO performs well against ITD when the calibration process is optimally performed.

Outcomes of critically ill patients with cirrhosis admitted to intensive care: an important perspective from the non-transplant setting.

BACKGROUND: Hospital admissions for cirrhosis have been increasing in the United Kingdom, leading to increased pressure on intensive care (ICU) services. Outcome data for patients admitted to ICU are currently limited to transplant centre reports, with mortality rates exceeding 70%. These tertiary reports could fuel a negative bias when patients with cirrhosis are reviewed for ICU admission in secondary care. AIMS: To determine whether disease severity and mortality rates in non-transplant general ICU are less severe than those reported by tertiary datasets. METHODS: A prospective dual-centre non-transplant ICU study. Admissions were screened for cirrhosis and physiological and biochemical data were collected. Disease-specific and critical illness scoring systems were evaluated. RESULTS: Cirrhosis was present in 137/4198 (3.3%) of ICU admissions. ICU and hospital mortality were 38% and 47%, respectively; median age 50 [43-59] years, 68% men, 72% alcoholic cirrhosis, median Child Pugh Score (CPS) 10 [8-11], Model for End-Stage Liver Disease (MELD) 18 [12-24], Acute Physiology and Chronic Health Evaluation II score (APACHE II) 16 [13-22]. CONCLUSIONS: Mortality rates and disease staging were notably lower than in the published literature, suggesting that patients have a more favourable outlook than previously considered. Transplant centre data should therefore be interpreted with caution when evaluating the merits of intensive care admission for patients in general secondary care ICUs.