Extracorporeal membrane oxygenation as a bridge to lung transplantation: a long-term study.

OBJECTIVES: We investigated early outcomes in patients with end-stage pulmonary disease bridged with extracorporeal membrane oxygenation (ECMO) with the intention to perform lung transplantation (LTx). METHODS: ECMO was used as a bridge to LTx in 20 patients between 2005 and 2013. Most patients suffered from rapid progress of disease and most failed to stabilize on mechanical ventilation. Sixteen patients (10 males, median age 42 years, range 25-59) underwent LTx after ECMO support for a median of 9 (range 1-229) days. Most patients were not on the waiting list while receiving ECMO, but after being assessed were on the waiting list for a median of 6 (range 1-72) days before LTx or death occurred. Median follow-up at 535 (range 36-3074) days was 100% complete, 9 patients have been followed for >1 year and 4 patients have been bridged during 2013. RESULTS: Four patients died on ECMO waiting for a donor and as intention-to-treat, the success for bridging was 80% (16/20) and 1-year survival was 62% (10/16, not including 4 with <1-year follow-up). For those who underwent LTx, 3 patients died in-hospital after LTx on Days 0, 16 and 82, respectively, and currently, 11/16 (69%) are alive and 1-year survival for transplanted patients was 9/12 (75%). Median ICU stay before and after LTx was 9 (range 2-229) days and 20 (range 0-53) days, respectively. At follow-up, lung function was evaluated, and mean forced expiratory volume at 1 s and forced vital capacity were 56±22% of predicted and 74±24% of predicted, respectively. CONCLUSIONS: ECMO used as a bridge to LTx results in acceptable survival in selected patients with end-stage pulmonary disease.

Usefulness of extracorporeal membrane oxygenation as a bridge to lung transplantation: a descriptive study.

BACKGROUND: This retrospective study investigated early outcome in patients with end-stage pulmonary disease bridged with extracorporeal membrane oxygenation (ECMO) with the intention of lung transplantation (LTx) in 2 Scandinavian transplant centers. METHODS: ECMO was used as a bridge to LTx in 16 patients between 2005 and 2009 at Sahlgrenska and Helsinki University Hospitals. Most patients were late referrals for LTx, and all failed to stabilize on mechanical ventilation. Thirteen patients (7 men) who were a mean age of 41 ± 8 years (range, 25-51 years) underwent LTx after a mean ECMO support of 17 days (range, 1-59 days). Mean follow-up at 25 ± 19 months was 100% complete. RESULTS: Three patients died on ECMO while waiting for a donor, and 1 patient died 82 days after LTx; thus, by intention-to-treat, the success for bridging is 81% and 1-year survival is 75%. All other patients survived, and 1-year survival for transplant recipients was 92% ± 7%. Mean intensive care unit stay after LTx was 28 ± 18 days (range, 3-53 days). All patients were doing well at follow-up; however, 2 patients underwent retransplantation due to bronchiolitis obliterans syndrome at 13 and 21 months after the initial ECMO bridge to LTx procedure. Lung function was evaluated at follow-up, and mean forced expiratory volume in 1 second was 2.0 ± 0.7 l (62% ± 23% of predicted) and forced vital capacity was 3.1 ± 0.6 l (74% ± 21% of predicted). CONCLUSION: ECMO used as a bridge to LTx results in excellent short-term survival in selected patients with end-stage pulmonary disease.

Effects of norepinephrine on renal perfusion, filtration and oxygenation in vasodilatory shock and acute kidney injury.

PURPOSE: The use of norepinephrine (NE) in patients with volume-resuscitated vasodilatory shock and acute kidney injury (AKI) remains the subject of much debate and controversy. The effects of NE-induced variations in mean arterial blood pressure (MAP) on renal blood flow (RBF), oxygen delivery (RDO(2)), glomerular filtration rate (GFR) and the renal oxygen supply/demand relationship (renal oxygenation) in vasodilatory shock with AKI have not been previously studied. METHODS: Twelve post-cardiac surgery patients with NE-dependent vasodilatory shock and AKI were studied 2-6 days after surgery. NE infusion rate was randomly and sequentially titrated to target MAPs of 60, 75 and 90 mmHg. At each target MAP, data on systemic haemodynamics, RBF, GFR and renal oxygen extraction were obtained by pulmonary artery catheter, by the renal vein thermodilution technique and by renal extraction of (51)Cr-ethylenediamine tetraacetic acid ((51)Cr-EDTA), respectively. RESULTS: At target MAP of 75 mmHg, RDO(2) (13%), GFR (27%) and urine flow were higher and renal oxygen extraction was lower (-7.4%) compared with at target MAP of 60 mmHg. However, the renal variables did not differ when compared at target MAPs of 75 and 90 mmHg. Cardiac index increased dose-dependently with NE. CONCLUSIONS: Restoration of MAP from 60 to 75 mmHg improves renal oxygen delivery, GFR and the renal oxygen supply/demand relationship in post-cardiac surgery patients with vasodilatory shock and AKI. This pressure-dependent renal perfusion, filtration and oxygenation at levels of MAP below 75 mmHg reflect a more or less exhausted renal autoregulatory reserve.

Acute renal failure is NOT an "acute renal success"--a clinical study on the renal oxygen supply/demand relationship in acute kidney injury.

OBJECTIVES: Acute kidney injury occurs frequently after cardiac or major vascular surgery and is believed to be predominantly a consequence of impaired renal oxygenation. However, in patients with acute kidney injury, data on renal oxygen consumption (RVO2), renal blood flow, glomerular filtration, and renal oxygenation, i.e., the renal oxygen supply/demand relationship, are lacking and current views on renal oxygenation in the clinical situation of acute kidney injury are presumptive and largely based on experimental studies. DESIGN: Prospective, two-group comparative study. SETTING: Cardiothoracic intensive care unit of a tertiary center. PATIENTS: Postcardiac surgery patients with (n = 12) and without (n = 37) acute kidney injury were compared with respect to renal blood flow, glomerular filtration, RVO2, and renal oxygenation. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Data on systemic hemodynamics (pulmonary artery catheter) and renal variables were obtained during two 30-min periods. Renal blood flow was measured using two independent techniques: the renal vein thermodilution technique and the infusion clearance of paraaminohippuric acid, corrected for renal extraction of paraaminohippuric acid. The filtration fraction was measured by the renal extraction of Cr-EDTA and the renal sodium resorption was measured as the difference between filtered and excreted sodium. Renal oxygenation was estimated from the renal oxygen extraction. Cardiac index and mean arterial pressure did not differ between the two groups. In the acute kidney injury group, glomerular filtration (-57%), renal blood flow (-40%), filtration fraction (-26%), and sodium resorption (-59%) were lower, renal vascular resistance (52%) and renal oxygen extraction (68%) were higher, whereas there was no difference in renal oxygen consumption between groups. Renal oxygen consumption for one unit of reabsorbed sodium was 2.4 times higher in acute kidney injury. CONCLUSIONS: Renal oxygenation is severely impaired in acute kidney injury after cardiac surgery, despite the decrease in glomerular filtration and tubular workload. This was caused by a combination of renal vasoconstriction and tubular sodium resorption at a high oxygen demand.

Dopamine increases renal oxygenation: a clinical study in post-cardiac surgery patients.

BACKGROUND: Imbalance of the renal medullary oxygen supply/demand relationship can cause ischaemic acute renal failure (ARF). The use of dopamine for prevention/treatment of ischaemic ARF has been questioned. It has been suggested that dopamine may increase renal oxygen consumption (RVO(2)) due to increased solute delivery to tubular cells, which may jeopardize renal oxygenation. Information on the effects of dopamine on renal perfusion, filtration and oxygenation in man is, however, lacking. We evaluated the effects of dopamine on renal blood flow (RBF), glomerular filtration rate (GFR), RVO(2) and renal O(2) demand/supply relationship, i.e. renal oxygen extraction (RO(2)Ex). METHODS: Twelve uncomplicated, mechanically ventilated and sedated post-cardiac surgery patients with pre-operatively normal renal function were studied. Dopamine was sequentially infused at 2 and 4 ug/kg/min. Systemic haemodynamics were evaluated by a pulmonary artery catheter. Absolute RBF was measured using two independent techniques: by the renal vein thermodilution technique and by infusion clearance of paraaminohippuric acid (PAH), with a correction for renal extraction of PAH. The filtration fraction (FF) was measured by the renal extraction of (51)Cr-EDTA. RESULTS: Neither GFR, tubular sodium reabsorption nor RVO(2) was affected by dopamine, which increased RBF (45-55%) with both methods, decreased renal vascular resistance (30-35%), FF (21-26%) and RO(2)Ex (28-34%). The RBF/CI ratio increased with dopamine. Dopamine decreased renal PAH extraction, suggestive of a flow distribution to the medulla. CONCLUSIONS: In post-cardiac surgery patients, dopamine increases the renal oxygenation by a pronounced renal pre-and post-glomerular vasodilation with no increases in GFR, tubular sodium reabsorption or renal oxygen consumption.

Effects of mannitol alone and mannitol plus furosemide on renal oxygen consumption, blood flow and glomerular filtration after cardiac surgery.

OBJECTIVE: Imbalance of the renal medullary oxygen supply/demand relationship can cause hypoxic medullary damage and ischaemic acute renal failure (ARF). The use of mannitol for prophylaxis/treatment of clinical ischaemic ARF is controversial and the effect of mannitol on renal oxygenation in man has not yet been investigated. We evaluated the effects of mannitol on renal oxygen consumption (RVO(2))(,) renal blood flow (RBF) and glomerular filtration rate (GFR) in postoperative patients. DESIGN: Prospective interventional study. SETTING: University hospital cardiothoracic ICU. PATIENTS: Ten uncomplicated mechanically ventilated and sedated postcardiac surgery patients with preoperatively normal renal function. INTERVENTIONS: Mannitol infusion (225 mg/kg + 75 mg/kg/h) and combined mannitol and furosemide infusion (0.25 mg/kg + 0.25 mg/kg/h). MEASUREMENTS AND RESULTS: Systemic haemodynamics were evaluated by a pulmonary artery catheter. RBF and GFR were measured by the renal vein thermodilution technique and by renal extraction of (51)Cr-EDTA, respectively. Mannitol increased urine flow (60%), GFR (20%) and filtration fraction (FF) (20%) with no change in RBF. This was accompanied by an increase in renal sodium reabsorption (18%), RVO(2) (19%) and renal oxygen extraction (21%). When combined with mannitol, furosemide normalised sodium reabsorption, RVO(2), renal oxygen extraction with no change in RBF, while GFR and FF were still elevated compared to control. CONCLUSIONS: In patients with normal renal function, mannitol increases GFR, which increases tubular sodium load, sodium reabsorption and RVO(2) after cardiac surgery. The lack of effect on RBF, indicates that mannitol impairs the renal oxygen supply/demand relationship. Furosemide normalised renal oxygenation when combined with mannitol.

Differential effects of human atrial natriuretic peptide and furosemide on glomerular filtration rate and renal oxygen consumption in humans.

OBJECTIVE: Imbalance in the renal medullary oxygen supply/demand relationship can cause hypoxic medullary damage and ischemic acute renal failure. Human atrial natriuretic peptide (h-ANP) increases glomerular filtration rate in clinical acute renal failure. This would increase renal oxygen consumption due to increased tubular load of sodium. Loop diuretics are commonly used in acute renal failure. Data on the effects of loop diuretics on glomerular filtration rate and renal oxygen consumption in humans are, however, controversial. We evaluated the effects of h-ANP and furosemide on renal oxygen consumption, glomerular filtration rate, and renal hemodynamics in humans. DESIGN AND SETTING: Prospective two-agent interventional study in a university hospital cardiothoracic ICU. PATIENTS: Nineteen uncomplicated, mechanically ventilated postcardiac surgery patients with normal renal function. INTERVENTIONS: h-ANP (25 and 50 ng/kg per minute, n=10) or furosemide (0.5 mg/kg per hour, n=9). MEASUREMENTS AND RESULTS: Renal plasma flow and glomerular filtration rate were measured using the infusion clearance technique for (51)Cr-labeled EDTA and paraaminohippurate, corrected for by renal extraction of PAH. h-ANP increased glomerular filtration rate, renal filtration fraction, fractional excretion of sodium, and urine flow. This was accompanied by an increase in tubular sodium reabsorption (9%) and renal oxygen consumption (26%). Furosemide infusion caused a 10- and 15-fold increase in urine flow and fractional excretion of sodium, respectively, accompanied by a decrease in tubular sodium reabsorption (-28%), renal oxygen consumption (-23%), glomerular filtration rate and filtration fraction (-12% and -7%, respectively). CONCLUSIONS: The filtered load of sodium is an important determinant of renal oxygen consumption. h-ANP improves glomerular filtration rate but does not have energy-conserving tubular effects. In contrast, furosemide decreases tubular sodium reabsorption and renal oxygen consumption and thus has the potential to improve the oxygen supply/demand relationship in clinical ischemic acute renal failure.

Bedside estimation of absolute renal blood flow and glomerular filtration rate in the intensive care unit. A validation of two independent methods.

OBJECTIVE: To evaluate various treatment strategies in critically ill patients with ischaemic acute renal failure, there is a need for reliable bedside measurements of total renal blood flow (RBF), glomerular filtration rate (GFR) and renal oxygen consumption without the need for urine collection. DESIGN: The continuous renal vein thermodilution method and the infusion clearance techniques were validated against the gold standard technique, the urinary clearance of paraaminohippurate (PAH) and chromium ethylenediaminetetraacetic acid, respectively. SETTING: University hospital cardiothoracic ICU. PATIENTS: Seventeen uncomplicated mechanically ventilated post-cardiac surgical patients. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Renal blood flow, GFR and the renal filtration fraction (FF) were measured for two consecutive 30-min periods by urinary clearance and compared with simultaneous measurements made by the thermodilution and infusion clearance techniques. Urinary clearance for PAH was corrected for by renal extraction of PAH. The within-group error, repeatability coefficient and the coefficient of variation were highest for the thermodilution technique and lowest for the infusion clearance technique with regard to RBF, GFR and FF. The infusion clearance technique had a higher agreement with the urinary clearance method than the thermodilution method. For estimations of RBF and GFR, the between-group errors were 33% and 43% comparing infusion clearance with urinary clearance and 65% and 67% comparing thermodilution with urinary clearance. CONCLUSIONS: The infusion clearance method had the highest reproducibility and the highest agreement with the urinary clearance reference method. The renal vein thermodilution technique is less reliable in the ICU setting due to poor repeatability and poor agreement with the reference method.

Recombinant human atrial natriuretic peptide in ischemic acute renal failure: a randomized placebo-controlled trial.

OBJECTIVE: Acute renal failure is associated with significant morbidity and mortality rates. Need for dialysis is an independent risk factor for early mortality after complicated cardiac surgery. Human atrial natriuretic peptide (h-ANP) is a potent endogenous natriuretic and diuretic substance. Exogenous administration of h-ANP increases glomerular filtration rate and renal blood flow in clinical acute renal failure. We have studied the effects of h-ANP on renal outcome in ischemic acute renal failure. DESIGN: A prospective, double-blind, randomized, placebo-controlled study. SETTING: Cardiothoracic intensive care units of two tertiary care centers. PATIENTS: Sixty-one patients with normal preoperative renal function suffering from postcardiac surgical heart failure requiring significant inotropic and vasoactive support. INTERVENTIONS: The patients were randomized to receive a continuous infusion of either recombinant h-ANP (50 ng.kg(-1).min(-1)) or placebo when serum creatinine increased by >50% from baseline. The treatment with h-ANP/placebo continued until serum creatinine decreased below the trigger value for inclusion or the patients fulfilled predefined criteria for dialysis. MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was dialysis on or before day 21 after the start of treatment. Secondary renal outcome variables were dialysis-free survival at day 21 and creatinine clearance. Twenty-nine patients were assigned h-ANP and 30 placebo. Six (21%) patients in the h-ANP group compared with 14 (47%) in the placebo group needed dialysis before or at day 21 (hazard ratio, 0.28; 95% confidence interval, 0.10-0.73; p =.009). Eight (28%) patients in the h-ANP group compared with 17 (57%) in the placebo group suffered from the combined end point dialysis or death before or at day 21 (hazard ratio, 0.35; 95% confidence interval, 0.14-0.82; p =.017). h-ANP improved creatinine clearance in contrast to placebo (p =.040). CONCLUSIONS: Infusion of h-ANP at a rate of 50 ng.kg(-1).min(-1) enhances renal excretory function, decreases the probability of dialysis, and improves dialysis-free survival in early, ischemic acute renal dysfunction after complicated cardiac surgery.