Nicholas M. Selby

Hemodialysis-Induced Cardiac Injury: Determinants and Associated Outcomes

BACKGROUND AND OBJECTIVES Hemodialysis (HD)-induced myocardial stunning driven by ischemia is a recognized complication of HD, which can be ameliorated by HD techniques that improve hemodynamics. In nondialysis patients, repeated ischemia leads to chronic reduction in left ventricular (LV) function. HD may initiate and drive the same process. In this study, we examined the prevalence and associations of HD-induced repetitive myocardial injury and long-term effects on LV function and patient outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Seventy prevalent HD patients were assessed for evidence of subclinical myocardial injury at baseline using serial echocardiography and followed up after 12 mo. Intradialytic blood pressure, hematologic and biochemical samples, and patient demographics were also collected at both time points. RESULTS Sixty-four percent of patients had significant myocardial stunning during HD. Age, ultrafiltration volumes, intradialytic hypotension, and cardiac troponin-T (cTnT) levels were independent determinants associated with its presence. Myocardial stunning was associated with increased relative mortality at 12 mo (P = 0.019). Cox regression analysis showed increased hazard of death in patients with myocardial stunning and elevated cTnT than in patients with elevated cTnT alone (P < 0.02). Patients with myocardial stunning who survived 12 mo had significantly lower LV ejection fractions at rest and on HD (P < 0.001). CONCLUSIONS HD-induced myocardial stunning is common, and may contribute to the development of heart failure and increased mortality in HD patients. Enhanced understanding of dialysis-induced cardiac injury may provide novel therapeutic targets to reduce currently excessive rates of cardiovascular morbidity and mortality.

Hemodialysis-Induced Cardiac Dysfunction Is Associated with an Acute Reduction in Global and Segmental Myocardial Blood Flow

BACKGROUND AND OBJECTIVES Hemodialysis is associated with hemodynamic instability, acute cardiac ischemia, and the development of regional wall motion abnormalities (RWMAs). This study used serial intradialytic H(2)(15)O positron emission tomography scanning to confirm that the development of dialysis-induced RWMAs was associated with reduction in myocardial blood flow (MBF). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Four prevalent hemodialysis patients without angiographically significant coronary artery disease had measurements of MBF during standard hemodialysis and biofeedback dialysis. All patients underwent serial measurements of MBF using positron emission tomography. Concurrent echocardiography was used to assess left ventricular function and the development of RWMAs. Hemodynamic variables were measured using continuous pulse wave analysis. RESULTS Mean prehemodialysis MBF was within the normal range. Global MBF was acutely reduced during hemodialysis. Segmental MBF was reduced to a significantly greater extent in areas that developed RWMAs compared with those that did not. Not all regions with reduced MBF were functionally affected, but a reduction in myocardial blood flow of >30% from baseline was significantly associated with the development of RWMAs. No significant differences in hemodynamic tolerability, RWMA development, or MBF between dialysis modalities were observed. CONCLUSIONS Hemodialysis is associated with repetitive myocardial ischemia, which, in the absence of coronary artery disease, may be due to coronary microvascular dysfunction. Stress-induced segmental left ventricular dysfunction correlates with matched reduction in MBF. Functional poststress recovery is consistent with myocardial stunning induced by hemodialysis. This process may be important in the development of heart failure in long-term hemodialysis patients.

Hemodialysis-Induced Repetitive Myocardial Injury Results in Global and Segmental Reduction in Systolic Cardiac Function

BACKGROUND AND OBJECTIVES Hemodialysis (HD)-induced regional wall motion abnormalities (RWMAs) are common in HD patients and driven by ischemia. In nondialysis patients, repeated ischemia leads to chronic reduction in left ventricular (LV) function. HD-induced myocardial ischemia may initiate the same process. We examined the effect of HD-induced repetitive myocardial stunning on global and regional LV function. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS We analyzed data from 30 patients, previously identified as developing HD-induced myocardial ischemia. Serial echocardiographic assessments of global and regional LV performance were performed at baseline and repeated after 12 mo. RESULTS Several patients developed segments with a fixed reduction in systolic function of >60% after 1 yr. In this patient group, there was a significant reduction in resting LV ejection fraction (EF) from 61.5 +/- 10.1% to 52.9 +/- 8.6% (P < 0.007). Peak LV EF in response to dialysis also decreased from 59.5 +/- 10% versus 49.9 +/- 6.5% (P < 0.003), with a consequent increase in HD-induced hypotension (P < 0.0001). CONCLUSIONS HD-induced myocardial stunning may progress over 12 mo to the development of regional fixed systolic dysfunction, consistent with underlying myocardial hibernation and fibrosis. This may be an important and potentially modifiable process in the development of heart failure in HD patients.

A Meta-analysis of Hemodialysis Catheter Locking Solutions in the Prevention of Catheter-Related Infection

BACKGROUND Catheter-related infection (CRI) is associated with increased all-cause mortality and morbidity in hemodialysis patients and may be reduced by using antimicrobial lock solutions (ALSs). STUDY DESIGN We performed a meta-analysis of studies identified from a search conducted in February 2007 of the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, databases of ongoing trials, major renal journals, and reference lists of relevant reports. SETTING & POPULATION Patients receiving acute or long-term hemodialysis through a tunneled or nontunneled central venous catheter. SELECTION CRITERIA FOR STUDIES We included all prospective randomized studies that compared ALS with heparin. INTERVENTION Administration of antibiotic and/or antimicrobial catheter locking solution. OUTCOME MEASURES Primary outcome was CRI rate in patients using ALSs compared with those using heparin alone. We also examined effects of ALS use on mortality, adverse events, and catheter thrombosis. RESULTS 7 studies were identified with a total of 624 patients and 819 catheters (448 tunneled, 371 nontunneled). CRI was 7.72 (95% confidence interval, 5.11 to 10.33) times less likely when using ALS. There were no consistent suggestions of adverse outcomes with ALS use; in particular, rates of catheter thrombosis did not increase. There was no evidence of antibiotic resistance developing during a maximum follow-up of 12 months. LIMITATIONS The major limitation of this review is the relatively short duration of follow-up of the included studies, which does not allow complete reassurance regarding the development of antibiotic resistance. Lack of direct comparisons means that determination of the most efficient ALS is not possible. CONCLUSIONS This review confirms that antibiotic locking solutions reduce the frequency of CRI without significant side effects.

Use of Electronic Results Reporting to Diagnose and Monitor AKI in Hospitalized Patients

BACKGROUND AND OBJECTIVES Many patients with AKI are cared for by non-nephrologists. This can result in variable standards of care that contribute to poor outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS To improve AKI recognition, a real-time, hospital-wide, electronic reporting system was designed based on current Acute Kidney Injury Network criteria. This system allowed prospective data collection on AKI incidence and outcomes such as mortality rate, length of hospital stay, and renal recovery. The setting was a 1139-bed teaching hospital with a tertiary referral nephrology unit. RESULTS An electronic reporting system was successfully introduced into clinical practice (false positive rate, 1.7%; false negative rate, 0.2%). The results showed that there were 3202 AKI episodes in 2619 patients during the 9-month study period (5.4% of hospital admissions). The in-hospital mortality rate was 23.8% and increased with more severe AKI (16.1% for stage 1 AKI versus 36.1% for stage 3) (P<0.001). More severe AKI was associated with longer length of hospital stay for stage 1 (8 days; interquartile range, 13) versus 11 days for stage 3 (interquartile range, 16) (P<0.001) and reduced chance of renal recovery (80.0% in stage 1 AKI versus 58.8% in stage 3) (P<0.001). Utility of the Acute Kidney Injury Network criteria was reduced in those with pre-existing CKD. CONCLUSIONS AKI is common in hospitalized patients and is associated with very poor outcomes. The successful implementation of electronic alert systems to aid early recognition of AKI across all acute specialties is one strategy that may help raise standards of care.

The Acute Cardiac Effects of Dialysis

It is well recognized that the procedure of hemodialysis is associated with significant changes in blood pressure and systemic hemodynamics; 20–30% of treatments are complicated by intradialytic hypotension (IDH). There are now an increasing number of studies using electrocardiographic, isotopic and echocardiographic techniques that show that subclinical myocardial ischemia occurs during dialysis. This concept is supported by some studies showing that dialysis can induce acute rises in troponins and creatinine kinase MB, although this has not been found by all authors. Some of this controversy may at least in part be due to the collection of blood samples immediately postdialysis, which is likely to be too early to reliably detect dialysis‐induced elevations of cardiac enzymes. Cardiovascular death is the biggest single cause of mortality in dialysis patients and of this sudden death comprises the largest proportion. As such, there is a large body of evidence examining whether dialysis is pro‐arrhythmogenic. It is clear that dialysis can increase QTc interval and QT dispersion and is capable of inducing arrhythmias on Holter monitoring, likely due to the interaction of multiple factors, some of which prime for the development of arrhythmias (particularly the presence of preexisting cardiac disease), and some of which act as triggers. However, the link between these electrocardiographic alterations and sudden death is relatively poorly studied. This review summarizes the available literature regarding the acute cardiac effects of dialysis in relation to the above, and discusses how these acute changes may contribute to the genesis of uremic cardiomyopathy and longer term cardiac outcomes.

Dialysis-Induced Regional Left Ventricular Dysfunction Is Ameliorated by Cooling the Dialysate

Dialysis patients who develop cardiac failure have a poor prognosis. Recurrent subclinical myocardial ischemia is important in the genesis of heart failure in nondialysis patients. It has previously been demonstrated that subclinical ischemia occurs during hemodialysis; therefore, this study examined whether the improved stability of cool-temperature dialysis lessens this phenomenon. Ten patients who were prone to intradialytic hypotension entered a randomized, crossover study to compare the development of dialysis-induced left ventricular (LV) regional wall motion abnormalities (RWMA) at dialysate temperatures of 37 and 35 degrees C. Serial echocardiography with quantitative analysis was used to assess ejection fraction and regional systolic LV function. BP and hemodynamic variables were measured using continuous pulse wave analysis. The severity of thermal symptoms was scored using a simple questionnaire. Forty-nine new RWMA developed in nine patients during hemodialysis with dialysate at 37 degrees C (HD(37)), compared with thirteen RWMA that developed in four patients during HD(35) (odds ratio 3.8; 95% confidence interval 2.1 to 6.9). The majority of RWMA displayed improved function by 30 min after dialysis. Overall, regional systolic LV function was significantly more impaired during HD(37) (P < 0.001). BP was higher during HD(35), with fewer episodes of hypotension as a result of a higher peripheral resistance and no difference in stroke volume. The development of thermal symptoms was heterogeneous, with most patients tolerating HD(35) well. This study confirms previous findings of reversible LV RWMA that develop during hemodialysis. It also shows that this phenomenon can be ameliorated by reducing dialysate temperature, a simple intervention with no cost implications.

Categorization of the hemodynamic response to hemodialysis: The importance of baroreflex sensitivity

Intradialytic hypotension (IDH) remains an important cause of morbidity and mortality in hemodialysis (HD) patients. The baroreflex arc is under autonomic control and regulates blood pressure. This study aimed to investigate the contribution of impaired baroreflex sensitivity (BRS) to the pathophysiology of IDH. Thirty‐four chronic HD (12 IDH‐prone, 22 IDH‐resistant) patients underwent BRS measurement during HD with relative blood volume monitoring. During analysis, patients were separated into four age‐matched groups according to resting BRS≥4.5 ms/mmHg and hemodynamic stability. Resting BRS was extremely heterogenous (geometric mean BRS 5.78±1.41 [range 1.76–41.41] ms/mmHg). Relative blood volume reduction was well matched in all groups (mean reduction in relative blood volume for all patients −6.74%±0.86%, P>0.05). Thirty‐seven episodes of IDH occurred in the IDH prone, reduced BRS group. Patients with impaired resting BRS and prone to IDH had markedly different responses to HD as compared to the preserved BRS group, but the total peripheral resistance response was significantly lower than in the IDH‐resistant patients (15.9%±2.1% vs. 42.4%±3.0%, respectively, P<0.001). In those patients prone to IDH and with impaired resting BRS, percentage reduction in cardiac output at the end of HD highly correlated with reduction in relative blood volume (r=0.94, P=0.006). Hypotension during dialysis may be an important source of recurrent cardiac injury and early recognition of those patients prone to relative symptomatic and asymptomatic hypotension remains important. Impaired resting BRS and recognition of a suboptimal peripheral pressor response, appear to predict those patients most likely to undergo hemodynamic instability and may assist in the pursuit of this elusive goal.

PERITONEAL DIALYSIS IS NOT ASSOCIATED WITH MYOCARDIAL STUNNING

♦ Background: Hemodynamic changes during hemodialysis can precipitate subclinical myocardial ischemia, which over time contributes to the development of cardiac failure and is associated with a poor prognosis. Peritoneal dialysis (PD) is also associated with acute changes in systemic hemodynamics and a similarly high incidence of cardiovascular disease; we therefore sought to examine whether the hemodynamic effects of a PD exchange would be sufficient to induce subclinical myocardial ischemia. ♦ Methods: 10 patients on PD entered a prospective observational study to determine whether left ventricular (LV) regional wall motion abnormalities (RWMAs) developed following a dialysate exchange. Serial echocardiography with quantitative analysis was used to assess ejection fraction and regional systolic LV function (shortening fraction). Blood pressure (BP) and hemodynamic variables were measured using continuous pulse wave analysis. ♦ Results: We observed a very low frequency of RWMA development (5/100 regions). Only 1 patient had more than 1 RWMA and 6 patients were entirely unaffected. Overall mean shortening fraction increased when comparing pre and post values for both 2-chamber (from 3.06% ± 1.5% to 4.26% ± 1.3%, p = 0.001) and 4-chamber (from 3.00% ± 0.7% to 3.67% ± 0.9%, p = 0.021) analyses. Mean arterial pressure fell by a small degree during drainage of dialysate, with a larger rise in BP observed during instillation. These changes were driven by changes in peripheral resistance that fell during drainage and rose during instillation. ♦ Conclusions: In contrast to hemodialysis, the acute effects of PD do not result in subclinical myocardial ischemia.

Impact of Compliance with a Care Bundle on Acute Kidney Injury Outcomes: A Prospective Observational Study.

Background A recent report has highlighted suboptimal standards of care for acute kidney injury (AKI) patients in England. The objective of this study was to ascertain if improvement in basic standard of care by implementing a care bundle (CB) with interruptive alert improved outcomes in patients with AKI. Methods An AKI CB linked to electronic recognition of AKI, coupled with an interruptive alert, was introduced to improve basic care delivered to patients with AKI. Outcomes were compared in patients who had the CB completed within 24 hours (early CB group) versus those who didn’t have the CB completed or had it completed after 24 hours. Results In the 11-month period, 2297 patients had 2500 AKI episodes, with 1209 and 1291 episodes occurring before and after implementation of the AKI CB with interruptive alert, respectively. The CB was completed within 24 hours in 306 (12.2%) of AKI episodes. In-hospital case-fatality was significantly lower in the early CB group (18% versus 23.1%, p 0.046). Progression to higher AKI stages was lower in the early CB group (3.9% vs. 8.1%, p 0.01). In multivariate analysis, patients in the early CB group had lower odds of death at discharge (0.641; 95% CI 0.46, 0.891), 30 days (0.707; 95% CI 0.527, 0.950), 60 days (0.704; 95% CI 0.526, 0.941) and after a median of 134 days (0.771; 95% CI 0.62, 0.958). Conclusions Compliance with AKI CB was associated with a decrease in case-fatality and reduced progression to higher AKI stage. Further interventions are required to improve utilization of the CB.