Bolus intravenous 0.9% saline leads to interstitial permeability pulmonary edema in healthy volunteers.

PURPOSE: Bolus intravenous administration of 0.9% saline has been associated with the development of pulmonary edema, and increased mortality. An animal model has previously demonstrated that rapid intravenous administration of 0.9% saline was associated with non-hydrostatic lung injury with increased lung lavage protein. We hypothesized that this non-hydrostatic effect would also occur in human volunteers. METHODS: In a randomized, cross-over study of 14 healthy male subjects, the lung lavage protein concentration and cardiorespiratory effects of an intervention with rapid intravenous administration of 30 mL/kg of 0.9% saline were compared with sham intervention. Bronchoalveolar lavage (BAL) was performed after fluid administration. Doppler echocardiography, lung ultrasound, pulmonary function tests, and blood sampling were performed before and after each intervention. RESULTS: The BAL total protein concentration was greater after 0.9% saline administration than with sham (196.1 µg/mL (SD 87.6) versus 129.8 µg/mL (SD 55.4), respectively (p = 0.020). Plasma angiopoietin-2 concentration was also increased to 2.26 ng/mL (SD 0.87) after 0.9% saline administration compared with sham 1.53 ng/mL (SD 0.69) (p < 0.001). There were small increases in stroke volume (from 58 mL (IQR 51-74) to 66 mL (IQR 58-74), p = 0.045) and Doppler echocardiography left ventricle E/e' ratio (from 5.0 (IQR 4.5-6.0) to 5.7 (IQR 5.3-6.3), p = 0.007), but no changes to right ventricular function. CONCLUSION: Rapid intravenous administration of 0.9% saline leads to interstitial permeability pulmonary edema in healthy human volunteers. Further research is now warranted to understand these effects in critically ill patients.

Coagulation abnormalities, bleeding, thrombosis, and management of patients with acute liver failure in Australia and New Zealand.

BACKGROUND AND AIM: To study the management of coagulation and hematological derangements among severe acute liver failure (ALF) patients in Australia and New Zealand liver transplant intensive care units (ICUs). METHODS: Analysis of key baseline characteristics, etiology, coagulation and hematological tests, use of blood products, thrombotic complications, and clinical outcomes during the first ICU week. RESULTS: We studied 62 ALF patients. The first day median peak international normalized ratio was 5.5 (inter-quartile range [IQR] 3.8-8.7), median longest activated partial thromboplastin time was 62 s (IQR 44-87), and median lowest fibrinogen was 1.1 (IQR 0.8-1.6) g/L. Fibrinogen was only measured in 85% of patients, which was less than other tests (P < 0.0001). Median initial lowest platelet count was 83 (IQR 41-122) × 109 /L. Overall, 58% of patients received fresh frozen plasma, 40% cryoprecipitate, 35% platelets, and 15% prothrombin complex concentrate. Patients with bleeding complications (19%) had more severe overall hypofibrinogenemia and thrombocytopenia. Thrombotic complications were less common (10% of patients), were not associated with consistent patterns of abnormal hemostasis, and were not immediately preceded by clotting factor administration and half occurred only after liver transplantation surgery. CONCLUSION: In ALF patients admitted to dedicated Australia and New Zealand ICUs, fibrinogen was measured less frequently than other coagulation parameters but, together with platelets, appeared more relevant to bleeding risk. Blood products and procoagulant factors were administered to most patients at variable levels of hemostatic derangement, and bleeding complications were more common than thrombotic complications. This epidemiologic information and practice variability provide baseline data for the design and powering of interventional studies.

Transcranial Doppler waveform changes due to increased cerebrovascular resistance and raised intracranial pressure in a patient with cirrhosis: A difference in shapes, not in numbers.

We report and discuss a case that illustrate the clinical utility of transcranial Doppler (TCD) ultrasound in a patient with cirrhosis. A 43-year-old female presented with acute decompensation of cirrhosis with hepatic encephalopathy, requiring mechanical ventilation. TCD showed low diastolic flow velocities and high pulsatility index (PI) consistent with increased cerebrovascular resistance (CVR). The flow velocities and PI normalized over a period of few days and correlated well with neurological improvement after treatment. Subsequently, the patient developed a large intracerebral hemorrhage with mass effect. The TCD measurements in intracranial hypertension were similar to those with cirrhosis and hepatic encephalopathy. However, the windkessel notch in the systolic phase of TCD waveform, related to the distensibility of arterial wall, was absent during raised intracranial pressure (ICP). The absence of a windkessel notch may help to differentiate a high downstream resistance due to raised ICP from increased CVR.

Therapeutic plasma exchange does not reduce vasopressor requirement in severe acute liver failure: a retrospective case series.

BACKGROUND: In acute liver failure (ALF) therapeutic plasma exchange (TPE) improves laboratory measures of liver function. In patients with ALF requiring minimal vasoactive support TPE has also been shown to provide haemodynamic benefits including an increase in systemic blood pressure. However the haemodynamic effects of TPE in patients with severe ALF requiring moderate or high dose vasopressor therapy has not been reported. We retrospectively examined the haemodynamic effects of TPE in a cohort of patients with severe ALF requiring vasopressor therapy. METHODS: Physiological, laboratory and treatment data were collected on all patients with ALF who received TPE between January 2000 and December 2012. All patients were managed in the intensive care unit of a tertiary referral centre for ALF and liver transplantation. The primary outcome measures were changes in mean arterial pressure (MAP), vasopressor score and the ratio of vasopressor score to MAP (vasopressor dependency index (VDI)) from baseline prior to TPE through to 12 hours after completion of TPE. Secondary outcome measures were changes in other routinely collected physiological variables and laboratory results. Results are presented as median (interquartile range (IQR)). Outcome measures were evaluated using a mixed effect model. RESULTS: Thirty nine TPE were performed in 17 patients with ALF (13 paracetamol poisoning). All TPE were performed with a centrifugal apheresis system (duration 130 minutes (IQR 115 - 147.5), plasma volume removed 5.1% body weight (IQR 4.6 - 5.5). Baseline values for primary outcome measures were: MAP 82 mmHg (IQR 72 - 92.5), vasopressor score 8.35 (IQR 3.62 - 24.6) and VDI 0.10 (IQR 0.05 - 0.31). MAP was significantly higher immediately after TPE compared to baseline (p = 0.039), however when corrected for change in vasopressor requirement there was no significant change in VDI with TPE (p = 0.953). Twelve hours after TPE the MAP, vasopressor score and VDI were not significantly different from baseline (p = 0.563, p = 0.317 and p = 0.214 respectively). CONCLUSION: In this cohort of patients with severe ALF centrifugal TPE did not significantly affect vasopressor requirements.

A rare case of rapidly enlarging tracheal lobular capillary hemangioma presenting as difficult to ventilate acute asthma during pregnancy.

BACKGROUND: Lobular Capillary Hemangioma (LCH) is a benign tumour that is known to be hormone responsive and have a relatively high incidence during pregnancy, the most common site being the gingival surfaces. A tracheal origin for this tumour is extremely rare, with no case reported so far in this patient population, and the only reported clinical presentation of tracheal LCH in the literature is with haemoptysis. CASE PRESENTATION: We describe a case of a 23-year-old known asthmatic who presented at 32 weeks gestation with life-threatening respiratory failure resembling acute severe asthma, requiring invasive ventilation which was extremely difficult. This was subsequently found to be due to a large tracheal LCH producing a ball-valve phenomenon and predominantly expiratory airflow limitation similar to acute asthma. The endotracheal tube was advanced past the lesion under bronchoscopic guidance, and urgent Caesarean section performed due to foetal distress. The tumour was subsequently debulked and the trachea stented, facilitated by bi-femoral veno-venous extra-corporeal membrane oxygenation with relatively low dose of heparin. CONCLUSION: To our knowledge, this is the first report of a unique presentation and management of largest tracheal LCH so far occurring during pregnancy. Pulmonary and critical care physicians should be aware of this unique differential of refractory asthma, the aggressive nature of this benign tumour due to hormonal influences during pregnancy, and feasibility of using bi-femoral veno-venous extra-corporeal membrane oxygenation with low dose heparin as a rescue, given the high risk of bleeding.

Changes in Respiratory Mechanics With Trunk Inclination Differs Between Patients With ARDS With and Without Obesity.

BACKGROUND: Studies investigating the effect of trunk inclination on respiratory mechanics in mechanically ventilated patients with ARDS have reported postural differences in partition respiratory mechanics. Compared with more upright positions, the supine-flat position provided lower lung and chest wall elastance, allowing reduced driving pressures and end-inspiratory transpulmonary pressure. However, the effect of trunk inclination on respiratory mechanics in patients with obesity and ARDS is uncertain. RESEARCH QUESTION: Does the effect of change in posture on partition respiratory mechanics differ between patients with ARDS with and without obesity? STUDY DESIGN AND METHODS: In this single-center study, patients with ARDS with and without obesity were randomized into two 15-minute steps in which trunk inclination was changed from semi-recumbent (40° head up) to supine-flat (0°), or vice versa. At the end of each step partition respiratory mechanics, airway opening pressure and arterial blood gases were measured. Paired t test was used to examine respiratory mechanics and blood gas variables in each group. RESULTS: Forty consecutive patients were enrolled. Twenty were obese (BMI, 38.4 [34.5-42.3]), and 20 were non-obese (BMI, 26.6 [25.2-28.5]). In the patients with obesity, lung and chest wall elastance, driving pressure, inspiratory transpulmonary pressure, Paco2, and ventilatory ratio were lower supine than semi-recumbent (P < .001). Airways resistance was greater supine (P = .006). In the patients without obesity, only chest wall elastance was lower in supine vs semi-recumbent (P < .001). INTERPRETATION: In mechanically ventilated patients with ARDS and obesity, supine posture provided lower lung and chest wall elastance, and better CO2 clearance, than the semi-recumbent posture. CLINICAL TRIAL REGISTRATION: This study was registered with Australian New Zealand Clinical Trials Registry (ACTRN12623000794606).

Continuous renal replacement therapy and its impact on hyperammonaemia in acute liver failure.

OBJECTIVE: Hyperammonaemia contributes to complications in acute liver failure (ALF) and may be treated with continuous renal replacement therapy (CRRT), but current practice is poorly understood. DESIGN: We retrospectively analysed data for baseline characteristics, ammonia concentration, CRRT use, and outcomes in a cohort of Australian and New Zealand patients with ALF. SETTING: All liver transplant ICUs across Australia and New Zealand. PARTICIPANTS: Sixty-two patients with ALF. MAIN OUTCOME MEASURES: Impact of CRRT on hyperammonaemia and patient outcomes. RESULTS: We studied 62 patients with ALF. The median initial (first 24 h) peak ammonia was 132 µmol/L (interquartile range [IQR], 91-172), median creatinine was 165 µmol/L (IQR, 92-263) and median urea was 6.9 mmol/L (IQR, 3.1-12.0). Most patients (43/62, 69%) received CRRT within a median of 6 hours (IQR, 2-12) of ICU admission. At CRRT commencement, three-quarters of such patients did not have Stage 3 acute kidney injury (AKI): ten patients (23%) had no KDIGO creatinine criteria for AKI, 12 (28%) only had Stage 1, and ten patients (23%) had Stage 2 AKI. Compared with non-CRRT patients, those treated with CRRT had higher ammonia concentrations (median, 141 µmol/L [IQR, 102-198] v 91 µmol/L [IQR, 54-115]; P = 0.02), but a nadir Day 1 pH of only 7.25 (standard deviation, 0.16). Prevention of extreme hyperammonaemia (> 140 µmol/L) after Day 1 was achieved in 36 of CRRT-treated patients (84%) and was associated with transplant-free survival (55% v 13%; P = 0.05). CONCLUSION: In Australian and New Zealand patients with ALF, CRRT is typically started early, before Stage 3 AKI or severe acidaemia, and in the presence hyperammonaemia. In these more severely ill patients, CRRT use was associated with prevention of extreme hyperammonaemia, which in turn, was associated with increased transplant-free survival.

Efficacy and safety of 20% albumin fluid loading in healthy subjects: a comparison of four resuscitation fluids.

Recently, buffered salt solutions and 20% albumin (small volume resuscitation) have been advocated as an alternative fluid for intravenous resuscitation. The relative comparative efficacy and potential adverse effects of these solutions have not been evaluated. In a randomized, double blind, cross-over study of six healthy male subjects we compared the pulmonary and hemodynamic effects of intravenous administration of 30 ml/kg of 0.9% saline, Hartmann's solution and 4% albumin, and 6 ml/kg of 20% albumin (albumin dose equivalent). Lung tests (spirometry, ultrasound, impulse oscillometry, diffusion capacity, and plethysmography), two- to three-dimensional Doppler echocardiography, carotid applanation tonometry, blood gases, serum/urine markers of endothelial, and kidney injury were measured before and after each fluid bolus. Data were analyzed with repeated measures ANOVA with effect of fluid type examined as an interaction. Crystalloids caused lung edema [increase in ultrasound B line (P = 0.006) and airway resistance (P = 0.009)], but evidence of lung injury [increased angiopoietin-2 (P = 0.019)] and glycocalyx injury [increased syndecan (P = 0.026)] was only observed with 0.9% saline. The colloids caused greater left atrial stretch, decrease in lung volumes, and increase in diffusion capacity than the crystalloids, but without pulmonary edema. Stroke work increased proportionally to increase in preload with all four fluids (R2 = 0.71). There was a greater increase in cardiac output and stroke volume after colloid administration, associated with a reduction in afterload. Hartmann's solution did not significantly alter ventricular performance. Markers of kidney injury were not affected by any of the fluids administrated. Bolus administration of 20% albumin is both effective and safe in healthy subjects. NEW & NOTEWORTHY Bolus administration of 20% albumin is both effective and safe in healthy subjects when compared with other commonly available crystalloids and colloidal solution.

Characteristics, management and outcomes of patients with acute liver failure admitted to Australasian intensive care units.

OBJECTIVE: Acute liver failure (ALF) leads to severe illness and usually requires admission to the intensive care unit (ICU). Despite its importance, little is known about patients with ALF in Australia and New Zealand. DESIGN: Binational observational study to evaluate the aetiology, baseline characteristics, patterns of illness, management, and outcomes for patients with ALF admitted to Australian and New Zealand ICUs. SETTING: All six Australian and New Zealand ICUs in liver transplant centres submitted de-identified data for ten or more consecutive patients with ALF. Data were obtained from the clinical record and included baseline characteristics, aetiology, mode of presentation, illness severity, markers of liver failure, critical care interventions, utilisation of transplantation, and hospital outcome. RESULTS: We studied 62 patients with ALF. Paracetamol overdose (POD) was the underlying cause of ALF in 53% of patients (33/62), with staggered ingestion in 42% of patients (14/33). Among patients with POD, 70% (23/33) were young women, most had psychiatric diagnoses, and most presented relatively early with overt liver failure. This group were transplanted in only 6% of cases (2/33) and had an overall mortality of 24% (8/33). The remaining patients with ALF had less common conditions, such as hepatitis B and non-paracetamol drug-induced ALF. These patients presented later and exhibited less extreme evidence of acute hepatic necrosis. Transplantation was performed in 38% of patients (11/29) in this subgroup. The mortality of nontransplanted non-POD patients was 56% (10/18). Illness severity at ICU admission, initial requirement for organ support therapies and length of hospital stay were similar between patients with POD and non-POD ALF. CONCLUSION: POD is the major cause of ALF in Australian and New Zealand liver transplant centres and is a unique and separate form of ALF. It has a much lower associated mortality and treatment with liver transplantation than non-POD ALF. Non-POD patients have a poor prognosis in the absence of transplantation.

Bolus intravenous 0.9% saline, but not 4% albumin or 5% glucose, causes interstitial pulmonary edema in healthy subjects.

Rapid intravenous (iv) infusion of 0.9% saline alters respiratory mechanics in healthy subjects. However, the relative cardiovascular and respiratory effects of bolus iv crystalloid vs. colloid are unknown. Six healthy male volunteers were given 30 ml/kg iv 0.9% saline, 4% albumin, and 5% glucose at a rate of 100 ml/min on 3 separate days in a double-blinded, randomized crossover study. Impulse oscillometry, spirometry, lung volumes, diffusing capacity (DLCO), and blood samples were measured before and after fluid administration. Lung ultrasound B-line score (indicating interstitial pulmonary edema) and Doppler echocardiography indices of cardiac preload were measured before, midway, immediately after, and 1 h after fluid administration. Infusion of 0.9% saline increased small airway resistance at 5 Hz (P = 0.04) and lung ultrasound B-line score (P = 0.01) without changes in Doppler echocardiography measures of preload. In contrast, 4% albumin increased DLCO, decreased lung volumes, and increased the Doppler echocardiography mitral E velocity (P = 0.001) and E-to-lateral/septal e' ratio, estimated blood volume, and N-terminal pro B-type natriuretic peptide (P = 0.01) but not lung ultrasound B-line score, consistent with increased pulmonary blood volume without interstitial pulmonary edema. There were no significant changes with 5% glucose. Plasma angiopoietin-2 concentration increased only after 0.9% saline (P = 0.001), suggesting an inflammatory mechanism associated with edema formation. In healthy subjects, 0.9% saline and 4% albumin have differential pulmonary effects not attributable to passive fluid filtration. This may reflect either different effects of these fluids on active signaling in the pulmonary circulation or a protective effect of albumin.

Echocardiographic estimation of mean pulmonary artery pressure in critically ill patients.

BACKGROUND: Indirect assessment of mean pulmonary arterial pressure (MPAP) may assist management of critically ill patients with pulmonary hypertension and right heart dysfunction. MPAP can be estimated as the sum of echocardiographically derived mean right ventricular to right atrial systolic pressure gradient and right atrial pressure; however, this has not been validated in critically ill patients. METHODS: This prospective validation study was conducted in patients undergoing pulmonary artery catheterisation during intensive care admission. Pulmonary artery catheter (PAC) measurements of MPAP were contemporaneously compared to MPAP estimated utilising transthoracic echocardiography (TTE)-derived mean right ventricular to right atrial systolic pressure gradient added to invasively measured right atrial pressure. RESULTS: Of 53 patients assessed, 23 had estimable MPAP using TTE. The mean difference between TTE- and PAC-derived MPAP was 1.9 mmHg (SD 5.0), with upper and lower limits of agreement of 11.6 and -7.9 mmHg, respectively. The median absolute percentage difference between TTE- and PAC-derived MPAP was 7.5%. Inter-rater reliability assessment was performed for 15 patients, giving an intra-class correlation coefficient of 0.96 (95% confidence intervals, 0.89 to 0.99). CONCLUSIONS: This echocardiographic method of estimating MPAP in critically ill patients was not equivalent to invasively measured MPAP, based on our predefined clinically acceptable range (±5 mmHg). The accuracy of this method in critically ill patients was similar to the results obtained in ambulatory patients and compared favourably with regard to the accuracy with echocardiographic estimation of systolic pulmonary arterial pressure. The utility of this technique is limited by frequent inability to obtain an adequate tricuspid regurgitant time-velocity integral in critically ill patients.

Refractory hypoxemia in a 23-year-old patient with Budd-Chiari syndrome.

Antiphospholipid syndrome is an autoimmune disorder characterized by a hypercoagulable state, leading to arterial and venous thrombosis. We present a 23-year-old patient, suspected of having Budd-Chiari syndrome due to antiphospholipid syndrome, who developed severe and progressive hypoxemia, requiring prolonged mechanical ventilation. After a detailed but unsuccessful workup, a contrast CT scan revealed an occluded superior vena cava and azygos vein-superior vena cava junction and massive right-to-left shunting through a network of systemic to pulmonary venous collaterals. Restoring normal blood flow from the azygos vein into the right atrium by stenting the azygos-superior vena cava junction resolved the hypoxemia immediately. Within the same procedure, the hepatic outflow obstruction was successfully treated by stenting a severe stenosis of the suprahepatic inferior vena cava caused by calcified thrombus.