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Danish Medical Journal Mar 2018During conventional cardiopulmonary bypass (CPB) there is no active perfusion of the pulmonary circulation and the mechanical ventilation is ceased leaving the lungs... (Review)
Review
During conventional cardiopulmonary bypass (CPB) there is no active perfusion of the pulmonary circulation and the mechanical ventilation is ceased leaving the lungs exposed to warm ischemia. Pulmonary dysfunction is seen in varying degrees after major surgery, but more severe in cardiac surgery patients probably due to the effects of CPB. The evidence for effect and safety are limited, but active pulmonary artery perfusion during CPB could be beneficial for the patients' postoperative oxygenation. Our aim was in a randomised clinical trial to assess primarily the effect of pulmonary artery perfusion during CPB on postoperative oxygenation in patients diagnosed with chronic obstructive pulmonary disease (COPD), secondarily to assess other possible benefits and harms. Furthermore, we wanted in a systematic review with meta-analyses of all randomised clinical trials to investigate the pooled effects of pulmonary artery perfusion during CPB. We planned and conducted a randomised, partly blinded, clinical trial assigning cardiac surgery patients diagnosed with COPD to receive pulmonary artery perfusion with oxygenated blood or histidine-tryptophan-ketoglutarate (HTK) solution compared to no pulmonary perfusion during CPB. The primary outcome was the oxygenation index measured during and after surgery. Secondary outcomes were intubation time, serious adverse events, days alive outside the intensive care unit and outside the hospital, 30- and 90-days mortality. Secondly, we conducted a systematic review of randomised clinical trials comparing benefits and harms of using pulmonary artery perfusion versus no pulmonary perfusion during CPB pooling results in meta-analyses and trial sequential analyses (TSA). Of the 90 randomised patients 89 were included in analysis of the primary outcome, the inverse oxygenation index, measured at a single time point 21 hours after CPB start and longitudinally 1, 3, 5, 7, and 21 hours after CPB start. At 21 hours, patients randomised to pulmonary artery perfusion with oxygenated blood had a higher inverse oxygenation index compared to patients randomised to no pulmonary perfusion during CPB (mean difference (MD) 0.94; 95% confidence interval (CI), 0.05 to 1.83; P=0.04). The inverse oxygenation index was also significantly higher at 21 hours after CPB start (MD 0.99; CI, 0.29 to 1.69; P=0.007), and longitudinally (P=0.009), for patients receiving pulmonary artery perfusion with oxygenated blood compared to pulmonary artery perfusion with HTK solution. This corresponds to a PaO difference of 23 mmHg with a median FiO of 0.32. We found no additional significant differences for the remaining comparisons of the inverse oxygenation index neither for any of the secondary outcomes. The systematic review identified 4 trials with a total of 210 patients. In meta-analyses pulmonary artery perfusion with blood versus no pulmonary perfusion during CPB was not associated with relative risk of death (1.7; 95% CI, 0.4 to 6.9; 210 patients in three trials with high and one trial with low risk of bias), serious adverse events (1.2; 95% CI, 0.8 to 1.8; 180 patients in two trials with high and one trial with low risk of bias) or intubation time (-0.4 hours; 95% CI, -1.1 to 0.4; 176 patients in three trials with high and one trial with low risk of bias). TSA on mortality, serious adverse events, and PaO/FiO ratio showed that required information sizes have not been reached, but pulmonary artery perfusion with blood was associated with a higher PaO/FiO ratio (27.8 mmHg; 95% CI, 5.7 to 50.0 mmHg; 119 patients in two trials with high and one trial with low risk of bias). TSA on intubation time showed that the boundary for lack of superiority (futility) was crossed refuting a shorten intubation time of 1.5 hours or more. Our trial provided additional knowledge about the use of pulmonary artery perfusion during CPB in cardiac surgery patients with COPD, and improved oxygenation for patients receiving pulmonary artery perfusion with oxygenated blood. Pulmonary artery perfusion with HTK solution did not result in an improved oxygenation. In line with this, the systematic review including data from additional trials showed a possible association between pulmonary artery perfusion with blood and improved oxygenation, but no significant associations with mortality, serious adverse events or intubation time. However, all data are too sparse to be conclusive.
Topics: Cardiac Surgical Procedures; Cardiopulmonary Bypass; Glucose; Hospital Mortality; Humans; Lung; Mannitol; Perfusion; Potassium Chloride; Procaine; Pulmonary Artery; Pulmonary Circulation; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Randomized Controlled Trials as Topic
PubMed: 29510817
DOI: No ID Found -
The Cochrane Database of Systematic... Sep 2017Perioperative fluid strategies influence clinical outcomes following major surgery. Many intravenous fluid preparations are based on simple solutions, such as normal... (Review)
Review
BACKGROUND
Perioperative fluid strategies influence clinical outcomes following major surgery. Many intravenous fluid preparations are based on simple solutions, such as normal saline, that feature an electrolyte composition that differs from that of physiological plasma. Buffered fluids have a theoretical advantage of containing a substrate that acts to maintain the body's acid-base status - typically a bicarbonate or a bicarbonate precursor such as maleate, gluconate, lactate, or acetate. Buffered fluids also provide additional electrolytes, including potassium, magnesium, and calcium, more closely matching the electrolyte balance of plasma. The putative benefits of buffered fluids have been compared with those of non-buffered fluids in the context of clinical studies conducted during the perioperative period. This review was published in 2012, and was updated in 2017.
OBJECTIVES
To review effects of perioperative intravenous administration of buffered versus non-buffered fluids for plasma volume expansion or maintenance, or both, on clinical outcomes in adults undergoing all types of surgery.
SEARCH METHODS
We electronically searched the Clinicaltrials.gov major trials registry, the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 6) in the Cochrane Library, MEDLINE (1966 to June 2016), Embase (1980 to June 2016), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to June 2016). We handsearched conference abstracts and, when possible, contacted leaders in the field. We reran the search in May 2017. We added one potential new study of interest to the list of 'Studies awaiting classification' and will incorporate this trial into formal review findings when we prepare the review update.
SELECTION CRITERIA
Only randomized controlled trials that compared buffered versus non-buffered intravenous fluids for surgical patients were eligible for inclusion. We excluded other forms of comparison such as crystalloids versus colloids and colloids versus different colloids.
DATA COLLECTION AND ANALYSIS
Two review authors screened references for eligibility, extracted data, and assessed risks of bias. We resolved disagreements by discussion and consensus, in collaboration with a third review author. We contacted trial authors to request additional information when appropriate. We presented pooled estimates for dichotomous outcomes as odds ratios (ORs) and for continuous outcomes as mean differences (MDs), with 95% confidence intervals (CIs). We analysed data via Review Manager 5.3 using fixed-effect models, and when heterogeneity was high (I² > 40%), we used random-effects models.
MAIN RESULTS
This review includes, in total, 19 publications of 18 randomized controlled trials with a total of 1096 participants. We incorporated five of those 19 studies (330 participants) after the June 2016 update. Outcome measures in the included studies were thematically similar, covering perioperative electrolyte status, renal function, and acid-base status; however, we found significant clinical and statistical heterogeneity among the included studies. We identified variable protocols for fluid administration and total volumes of fluid administered to patients intraoperatively. Trial authors variably reported outcome data at disparate time points and with heterogeneous patient groups. Consequently, many outcome measures are reported in small group sizes, reducing overall confidence in effect size, despite relatively low inherent bias in the included studies. Several studies reported orphan outcome measures. We did not include in the results of this review one large, ongoing study of saline versus Ringer's solution.We found insufficient evidence on effects of fluid therapies on mortality and postoperative organ dysfunction (defined as renal insufficiency leading to renal replacement therapy); confidence intervals were wide and included both clinically relevant benefit and harm: mortality (Peto OR 1.85, 95% CI 0.37 to 9.33; I² = 0%; 3 trials, 6 deaths, 276 participants; low-quality evidence); renal insufficiency (OR 0.82, 95% CI 0.34 to 1.98; I² = 0%; 4 trials, 22 events, 276 participants; low-quality evidence).We noted several metabolic differences, including a difference in postoperative pH measured at end of surgery of 0.05 units - lower in the non-buffered fluid group (12 studies with a total of 720 participants; 95% CI 0.04 to 0.07; I² = 61%). However, this difference was not maintained on postoperative day one. We rated the quality of evidence for this outcome as moderate. We observed a higher postoperative serum chloride level immediately after operation, with use of non-buffered fluids reported in 10 studies with a total of 530 participants (MD 6.77 mmol/L, 95% CI 3.38 to 10.17), and this difference persisted until day one postoperatively (five studies with a total of 258 participants; MD 8.48 mmol/L, 95% CI 1.08 to 15.88). We rated the quality of evidence for this outcome as moderate.
AUTHORS' CONCLUSIONS
Current evidence is insufficient to show effects of perioperative administration of buffered versus non-buffered crystalloid fluids on mortality and organ system function in adult patients following surgery. Benefits of buffered fluid were measurable in biochemical terms, particularly a significant reduction in postoperative hyperchloraemia and metabolic acidosis. Small effect sizes for biochemical outcomes and lack of correlated clinical follow-up data mean that robust conclusions on major morbidity and mortality associated with buffered versus non-buffered perioperative fluid choices are still lacking. Larger studies are needed to assess these relevant clinical outcomes.
Topics: Adult; Buffers; Crystalloid Solutions; Fluid Therapy; Hospital Mortality; Humans; Isotonic Solutions; Perioperative Care; Plasma Substitutes; Randomized Controlled Trials as Topic; Rehydration Solutions; Surgical Procedures, Operative
PubMed: 28933805
DOI: 10.1002/14651858.CD004089.pub3 -
The Cochrane Database of Systematic... Aug 2016The ideal intravenous fluid for kidney transplantation has not been defined, despite the common use of normal saline during the peri-operative period. The high chloride... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The ideal intravenous fluid for kidney transplantation has not been defined, despite the common use of normal saline during the peri-operative period. The high chloride content of normal saline is associated with an increased risk of hyperchloraemic metabolic acidosis, which may in turn increase the risk of hyperkalaemia and delayed graft function. Balanced electrolyte solutions have a lower chloride content which may decrease this risk and avoid the need for dialysis due to hyperkalaemia in the immediate post-transplant period. Randomised controlled trials (RCTs) addressing this issue have used biochemical outcomes to compare fluids and have been underpowered to address patient-centred outcomes such as delayed graft function.
OBJECTIVES
To examine the effect of lower-chloride solutions versus normal saline on delayed graft function, hyperkalaemia and acid-base status in kidney transplant recipients.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant's Specialised Register to 26 November 2015 through contact with the Information Specialist using search terms relevant to this review.
SELECTION CRITERIA
RCTs of kidney transplant recipients that compared peri-operative intravenous lower-chloride solutions to normal saline were included.
DATA COLLECTION AND ANALYSIS
Two independent investigators assessed studies for eligibility and risk of bias. Data from individual studies were extracted using standardised forms and pooled according to a published protocol. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes.
MAIN RESULTS
Six studies (477 participants) were included in the review. All participants were adult kidney transplant recipients and 70% of participants underwent live-donor kidney transplantation. The overall risk of bias was low for selection bias and unclear for remaining domains. There was no difference in the risk of delayed graft function (3 studies, 298 participants: RR 1.03, 95% CI 0.62 to 1.70) or hyperkalaemia (2 studies, 199 participants: RR 0.48, 95% CI 0.04 to 6.10) for participants who received balanced electrolyte solutions compared to normal saline. Intraoperative balanced electrolyte solutions compared to normal saline were associated with higher blood pH (3 studies, 193 participants: MD 0.07, 95% CI 0.05 to 0.09), higher serum bicarbonate (3 studies, 215 participants: MD 3.02 mEq/L, 95% CI 2.00 to 4.05) and lower serum chloride (3 studies, 215 participants: MD -9.93 mmol/L, 95% CI -19.96 to 0.11). There were four cases of graft loss in the normal saline group and one in the balanced electrolyte solution group, and four cases of acute rejection in the normal saline group compared to two cases in the balanced electrolyte solution group.
AUTHORS' CONCLUSIONS
Balanced electrolyte solutions are associated with less hyperchloraemic metabolic acidosis compared to normal saline, however it remains uncertain whether lower-chloride solutions lead to improved graft outcomes compared to normal saline.
Topics: Adult; Delayed Graft Function; Gluconates; Humans; Hydrogen-Ion Concentration; Hyperkalemia; Infusions, Intravenous; Isotonic Solutions; Kidney; Kidney Transplantation; Magnesium Chloride; Potassium Chloride; Ringer's Solution; Sodium Acetate; Sodium Chloride; Solutions
PubMed: 27502170
DOI: 10.1002/14651858.CD010741.pub2 -
The Cochrane Database of Systematic... May 2015Antihypertensive drugs from the thiazide diuretic drug class have been shown to reduce mortality and cardiovascular morbidity. Loop diuretics are indicated and used to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antihypertensive drugs from the thiazide diuretic drug class have been shown to reduce mortality and cardiovascular morbidity. Loop diuretics are indicated and used to treat hypertension, but a systematic review of their blood pressure-lowering efficacy or effectiveness in terms of reducing cardiovascular mortality or morbidity from randomized controlled trial (RCT) evidence has not been conducted.
OBJECTIVES
To determine the dose-related decrease in systolic or diastolic blood pressure, or both, as well as adverse events leading to participant withdrawal and adverse biochemical effects (serum potassium, uric acid, creatinine, glucose and lipids profile) due to loop diuretics versus placebo control in the treatment of people with primary hypertension.
SEARCH METHODS
We searched the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, 2014, Issue 9), MEDLINE, MEDLINE In-Process, EMBASE, and ClinicalTrials.gov to 27 October 2014.
SELECTION CRITERIA
We included double-blind randomized placebo-controlled trials of at least three weeks duration comparing loop diuretic with a placebo in people with primary hypertension defined as blood pressure greater than 140/90 mmHg at baseline.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the risk of bias and extracted data. We used weighted mean difference and a fixed effects model to combine continuous outcome data. We analysed the drop outs due to adverse effects using relative risk ratio.
MAIN RESULTS
Nine trials evaluated the dose-related blood pressure-lowering efficacy of five drugs within the loop diuretics class (furosemide 40 mg to 60 mg, cicletanine 100 mg to 150 mg, piretanide 3 mg to 6 mg, indacrinone enantiomer -2.5 mg to -10.0/+80 mg, and etozolin 200 mg) in 460 people with baseline blood pressure of 162/103 mmHg for a mean duration of 8.8 weeks. The best estimate of systolic/diastolic blood pressure-lowering efficacy of loop diuretics was -7.9 (-10.4 to -5.4) mmHg/ -4.4 (-5.9 to -2.8) mmHg. Withdrawals due to adverse effects and serum biochemical changes did not show a significant difference.We performed additional searches in 2012 and 2014, which found no additional trials meeting the minimum inclusion criteria.
AUTHORS' CONCLUSIONS
Based on the limited number of published RCTs, the systolic/diastolic blood pressure-lowering effect of loop diuretics is -8/-4 mmHg, which is likely an overestimate. We graded the quality of evidence for both systolic and diastolic blood pressure estimates as "low" due to the high risk of bias of included studies and the high likelihood of publication bias. We found no clinically meaningful blood pressure-lowering differences between different drugs within the loop diuretic class. The dose-ranging effects of loop diuretics could not be evaluated. The review did not provide a good estimate of the incidence of harms associated with loop diuretics because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.
Topics: Antihypertensive Agents; Blood Pressure; Dose-Response Relationship, Drug; Furosemide; Humans; Hypertension; Indans; Pyridines; Randomized Controlled Trials as Topic; Sodium Potassium Chloride Symporter Inhibitors; Sulfonamides; Thiazoles
PubMed: 26000442
DOI: 10.1002/14651858.CD003825.pub4 -
The Cochrane Database of Systematic... Feb 2015Blood transfusions are associated with significant morbidity and mortality. Prophylactic administration of loop diuretics (furosemide, bumetanide, ethacrynic acid, or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Blood transfusions are associated with significant morbidity and mortality. Prophylactic administration of loop diuretics (furosemide, bumetanide, ethacrynic acid, or torsemide) is common practice, especially among people who are at risk for circulatory overload, pulmonary oedema or both.
OBJECTIVES
This review aimed to determine if the prophylactic administration of loop diuretics (furosemide, bumetanide, ethacrynic acid, or torsemide) provides a therapeutic advantage (that is, a favourable risk benefit ratio) in adults and children who are recipients of any blood product transfusion versus placebo, no treatment, or general fluid restriction measures.
SEARCH METHODS
We searched the Cochrane Renal Group's Specialised Register to 13 January 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.
SELECTION CRITERIA
All randomised controlled trials (RCTs) and quasi-RCTs assessing a loop diuretic in patients receiving any blood transfusion were considered for inclusion.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed study quality and extracted data. Study authors were contacted for additional information. Results were to be expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Mean effect sizes were to be calculated using the random-effects models.
MAIN RESULTS
We included four studies that involved 100 participants. Furosemide was the only diuretic investigated in all four studies.None of the included studies assessed the clinically important outcomes noted in our protocol. The studies focused on various markers of respiratory function. An improvement in fraction of inspired oxygen (in favour of furosemide) was noted in one study. An improvement in pulmonary capillary wedge pressure (in favour of furosemide) was noted in two studies.
AUTHORS' CONCLUSIONS
There was insufficient evidence to determine whether premedicating people undergoing blood transfusion with loop diuretics prevents clinically important transfusion-related morbidity. Due to the continued use of prophylactic loop diuretics during transfusions, and because this review highlights the absence of evidence to justify this practice, well-conducted RCTs are needed. Given the high mortality, severe morbidity and increasing incidence of transfusion-associated circulatory overload, determining the therapeutic utility of pre-transfusion loop diuresis is an urgent need.
Topics: Adult; Body Water; Confidence Intervals; Furosemide; Humans; Infant, Newborn; Infant, Premature; Pulmonary Edema; Randomized Controlled Trials as Topic; Sodium Potassium Chloride Symporter Inhibitors; Transfusion Reaction
PubMed: 25685898
DOI: 10.1002/14651858.CD010138.pub2 -
British Journal of Clinical Pharmacology Apr 2015Hyponatraemia is one of the major adverse effects of thiazide and thiazide-like diuretics and the leading cause of drug-induced hyponatraemia requiring hospital... (Meta-Analysis)
Meta-Analysis
AIMS
Hyponatraemia is one of the major adverse effects of thiazide and thiazide-like diuretics and the leading cause of drug-induced hyponatraemia requiring hospital admission. We sought to review and analyze all published cases of this important condition.
METHODS
Ovid Medline, Embase, Web of Science and PubMed electronic databases were searched to identify all relevant articles published before October 2013. A proportions meta-analysis was undertaken.
RESULTS
One hundred and two articles were identified of which 49 were single patient case reports. Meta-analysis showed that mean age was 75 (95% CI 73, 77) years, 79% were women (95% CI 74, 82) and mean body mass index was 25 (95% CI 20, 30) kg m(-2) . Presentation with thiazide-induced hyponatraemia occurred a mean of 19 (95% CI 8, 30) days after starting treatment, with mean trough serum sodium concentration of 116 (95% CI 113, 120) mm and serum potassium of 3.3 (95% CI 3.0, 3.5) mm. Mean urinary sodium concentration was 64 mm (95% CI 47, 81). The most frequently reported drugs were hydrochlorothiazide, indapamide and bendroflumethiazide.
CONCLUSIONS
Patients with thiazide-induced hyponatraemia were characterized by advanced age, female gender, inappropriate saliuresis and mild hypokalaemia. Low BMI was not found to be a significant risk factor, despite previous suggestions. The time from thiazide initiation to presentation with hyponatraemia suggests that the recommended practice of performing a single investigation of serum biochemistry 7-14 days after thiazide initiation may be insufficient or suboptimal. Further larger and more systematic studies of thiazide-induced hyponatraemia are required.
Topics: Age Factors; Drug Monitoring; Female; Humans; Hyponatremia; Male; Sex Factors; Sodium Chloride Symporter Inhibitors
PubMed: 25139696
DOI: 10.1111/bcp.12499