The time of onset of intradialytic hypotension during a hemodialysis session associates with clinical parameters and mortality

Abstract

Intradialytic hypotension (IDH) is a common complication of hemodialysis, but there is no data about the time of onset during treatment. Here we describe the incidence of IDH throughout hemodialysis and associations of time of hypotension with clinical parameters and survival by analyzing data from 21 dialysis clinics in the United States to include 785682 treatments from 4348 patients. IDH was defined as a systolic blood pressure of 90 mmHg or under while IDH incidence was calculated in 30-minute intervals throughout the hemodialysis session. Associations of time of IDH with clinical and treatment parameters were explored using logistic regression and with survival using Cox-regression. Sensitivity analysis considered further IDH definitions. IDH occurred in 12% of sessions at a median time interval of 120-149 minutes. There was no notable change in IDH incidence across hemodialysis intervals (range: 2.6-3.2 episodes per 100 session-intervals). Relative blood volume and ultrafiltration volume did not notably associate with IDH in the first 90 minutes but did thereafter. Associations between central venous but not arterial oxygen saturation and IDH were present throughout hemodialysis. Patients prone to IDH early as compared to late in a session had worse survival. Sensitivity analyses suggested IDH definition affects time of onset but other analyses were comparable. Thus, our study highlights the incidence of IDH during the early part of hemodialysis which, when compared to later episodes, associates with clinical parameters and mortality. Intradialytic hypotension (IDH) is a common complication of hemodialysis, but there is no data about the time of onset during treatment. Here we describe the incidence of IDH throughout hemodialysis and associations of time of hypotension with clinical parameters and survival by analyzing data from 21 dialysis clinics in the United States to include 785682 treatments from 4348 patients. IDH was defined as a systolic blood pressure of 90 mmHg or under while IDH incidence was calculated in 30-minute intervals throughout the hemodialysis session. Associations of time of IDH with clinical and treatment parameters were explored using logistic regression and with survival using Cox-regression. Sensitivity analysis considered further IDH definitions. IDH occurred in 12% of sessions at a median time interval of 120-149 minutes. There was no notable change in IDH incidence across hemodialysis intervals (range: 2.6-3.2 episodes per 100 session-intervals). Relative blood volume and ultrafiltration volume did not notably associate with IDH in the first 90 minutes but did thereafter. Associations between central venous but not arterial oxygen saturation and IDH were present throughout hemodialysis. Patients prone to IDH early as compared to late in a session had worse survival. Sensitivity analyses suggested IDH definition affects time of onset but other analyses were comparable. Thus, our study highlights the incidence of IDH during the early part of hemodialysis which, when compared to later episodes, associates with clinical parameters and mortality. Intradialytic hypotension (IDH) associates with adverse outcomes in hemodialysis (HD) patients, including patient self-reported symptom burden, access failure, cardiovascular events, and mortality.1McIntyre C.W. Haemodialysis-induced myocardial stunning in chronic kidney disease—a new aspect of cardiovascular disease.Blood Purif. 2010; 29: 105-110Crossref PubMed Scopus (102) Google Scholar, 2Chang T. Paik J. Greene T. et al.Intradialytic hypotension and vascular access thrombosis.J Am Soc Nephrol. 2011; 22: 1526-1533Crossref PubMed Scopus (35) Google Scholar, 3Shoji T. Tsubakihara Y. Fujii M. et al.Hemodialysis associated hypotension as an independent risk factor for two-year mortality in hemodialysis patients.Kidney Int. 2004; 66: 1212-1220Abstract Full Text Full Text PDF PubMed Scopus (428) Google Scholar Despite being one of the most common complications associated with HD, there is no consensus on the definition, means to prevention, and management of IDH. The challenges in defining IDH have been reviewed elsewhere,4Assimon M.M. Flythe J.E. Definitions of intradialytic hypotension.Semin Dial. 2017; 30: 464-472Crossref PubMed Scopus (23) Google Scholar but generally definitions include some or all of the following: (i) a systolic blood pressure (SBP) nadir; (ii) an absolute reduction in SBP; and (iii) required interventions. Basic physiology suggests that reductions in blood pressure during HD can be related to a combination of volume reduction, impaired cardiac output response to fluid removal, and changes in total peripheral resistance.5Zucchelli P. Santoro A. Dialysis-induced hypotension: a fresh look at pathophysiology.Blood Purif. 1993; 11: 85-98Crossref PubMed Scopus (86) Google Scholar Unfortunately, it is not trivial to comprehensively monitor these parameters, so studies are scarce and include small numbers of patients.6Feng Y. Zou Y. Zheng Y. et al.The value of non-invasive measurement of cardiac output and total peripheral resistance to categorize significant changes of intradialytic blood pressure: a prospective study.BMC Nephrol. 2018; 19: 310Crossref PubMed Scopus (5) Google Scholar Interventions for managing IDH are lacking. There is increasing evidence that use of cooled dialysate can prevent IDH7Mustafa R.A. Bdair F. Akl E.A. et al.Effect of lowering the dialysate temperature in chronic hemodialysis: a systematic review and meta-analysis.Clin J Am Soc Nephrol. 2016; 11: 442-457Crossref PubMed Scopus (50) Google Scholar but as yet is not universally adopted. Other interventions, including use of relative blood volume (RBV),8Reddan D. Szczech L.A. Hasselbad V. et al.Intradialytic blood volume monitoring in ambulatory hemodialysis patients: a randomized trial.J Am Soc Nephrol. 2005; 16: 2162-2169Crossref PubMed Scopus (151) Google Scholar biofeedback-controlled ultrafiltration rate (UFR), and/or dialysate sodium9Leung K.C.W. Quinn R.R. Ravani P. et al.Randomized crossover trial of blood volume monitoring-guided ultrafiltration biofeedback to reduce intradialytic hypotensive episodes with hemodialysis.Clin J Am Soc Nephrol. 2017; 12: 1831-1840Crossref PubMed Scopus (23) Google Scholar and pharmacological management,10Chang T.I. Impact of drugs on intradialytic hypotension: antihypertensives and vasoconstrictors.Semin Dial. 2017; 30: 532-536Crossref PubMed Scopus (10) Google Scholar all lack a sufficient evidence base for widespread acceptance. Numerous factors have been shown to associate with IDH occurrence. These include demographic factors, comorbidities, treatment prescriptions, serum osmolality, antihypertensive medications, and anemia.11Chou J. Kalantar-Zadeh K. Mathew A. A brief review of intradialytic hypotension with a focus on survival.Semin Dial. 2017; 30: 473-480Crossref PubMed Scopus (43) Google Scholar, 12Singh A.T. Mc Causland F.R. Osmolality and blood pressure stability during hemodialysis.Semin Dial. 2017; 30: 509-517Crossref PubMed Scopus (15) Google Scholar, 13Larkin J.W. Reviriego-Mendoza M.M. Usvyat L.A. et al.To cool, or too cool: is reducing dialysate temperature the optimal approach to preventing intradialytic hypotension?.Semin Dial. 2017; 30: 501-508Crossref PubMed Scopus (6) Google Scholar RBV at the time of IDH has been shown to have significant intersubject variability, but for a given individual, there appears to be a relatively stable critical RBV preceding IDH.14Barth C. Boer W. Garzoni D. et al.Characteristics of hypotension-prone haemodialysis patients: is there a critical relative blood volume?.Nephrol Dial Transplant. 2003; 18: 1353-1360Crossref PubMed Scopus (90) Google Scholar There are some data to suggest that central venous oxygen saturation (ScvO2) decreases more in sessions where IDH occurs.15Perazzini C. Bolasco P.G. Corazza L. et al.Prediction of intradialytic hypotension based on oxygen saturation variations.Comput Cardiol. 2013; : 40:1223-1226Google Scholar Studies investigating IDH frequently define sessions based on whether an IDH event occurs, or define patients as being prone to IDH or not, but little attention has been given to how the incidence of IDH onset varies within the HD session. We aimed to: (i) characterize the incidence of IDH in discrete time intervals within an HD session; (ii) investigate whether any routinely collected parameters were associated with the time of IDH; and (iii) consider whether the time of IDH is associated with mortality. This was a retrospective, observational cohort study utilizing routinely collected treatment data from the network of Renal Research Institute clinics across the United States. We extracted data from all dialysis sessions in 21 clinics between January 1, 2017 and October 31, 2019 from both incident and prevalent patients, with no exclusion criteria. Parameters extracted included demographic and laboratory variables, comorbidities, HD prescriptions, and blood pressure, as well as hematocrit, RBV, and oxygen saturation (SO2), measured by the Crit-Line monitor (CLM; Fresenius Medical Care North America, Waltham, MA). The number of patients and sessions in these clinics during the study period determined the sample size. The study was deemed to be exempt from review by the Western Institutional Review Board. To comply with the US Health Insurance Portability and Accountability Act definition of a deidentified data set, patient age was capped at 90 years and dates were transformed to a relative timeline. The study was reported in accordance with Strengthening the Reporting of Observational Studies in Epidemiology guidance.16von Elm E. Altman D.G. Egger M. et al.The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.Lancet. 2007; 370: 1453-1457Abstract Full Text Full Text PDF PubMed Scopus (4680) Google Scholar An intradialytic SBP of <90 mm Hg has been shown to have the greatest association with mortality,17Flythe J.E. Xue H. Lynch K.E. et al.Association of mortality risk with various definitions of intradialytic hypotension.J Am Soc Nephrol. 2015; 26: 724-734Crossref PubMed Scopus (190) Google Scholar and we used this as our primary definition of IDH. Acknowledging the lack of consensus on IDH definition, we undertook sensitivity analyses with 3 other definitions of IDH. Assimon and Flythe4Assimon M.M. Flythe J.E. Definitions of intradialytic hypotension.Semin Dial. 2017; 30: 464-472Crossref PubMed Scopus (23) Google Scholar describe 3 main components of most definitions: characteristics of blood pressure behavior (largely a decline and/or a nadir value), interventions administered, and patient-reported symptoms. Furthermore, it is highlighted that definitions based on a nadir value only are likely to include events that relate to chronic hypotension, which will skew results to data had no on patient-reported so we aimed to the other components using 3 decline in SBP mm Hg from combination of a nadir SBP <90 mm Hg a decline in SBP mm Hg from based on during the definition based on administered, we the minutes of treatment data to of calculated the value for per session at to be the and defined IDH as any fluid of at the total fluid the for the given were defined as when an IDH occurred in of we all patients and sessions based on the of IDH. patients with at one IDH event were as prone to IDH more of IDH episodes occurred minutes and late onset HD sessions where an IDH session occurred were as early or late onset based on whether the first IDH in the session was or minutes. pressure were and minutes during the and when using to the dialysis and dialysis were from the of the first treatment session in the study are defined by for the and extracted included or of chronic failure, and peripheral use was defined as patients with at one antihypertensive in the first of the study and of data from the and for of were used to define as cardiovascular related or The hematocrit, and RBV was included as arterial oxygen saturation for all sessions where vascular access was a or and as for all sessions utilizing a central venous measurement of was we calculated the blood in throughout the treatment. This was based on the was to be was measured by in was calculated as the of oxygen per of was and oxygen was calculated using demographic A. et of the first 2010; PubMed Scopus Google Scholar on the this can be in from this H. M. et a Purif. PubMed Scopus Google Scholar To for the that can during a in a session where IDH occurs, we defined the for a given session as the of all preceding an IDH where an and the of all in a session where it did was to and reported as per that blood pressure were minutes and on it was not to define IDH any more to have occurred within a 30-minute we session to 30-minute intervals from to minutes and interval for minutes The primary was to describe the incidence of IDH throughout HD To the incidence of IDH in any given we the total number of IDH events in an interval by the total number of sessions where at one blood pressure measurement had been during that the first of IDH in any HD session was included in the To related to in of we calculated the incidence for at the and across IDH incidence was reported in of the intervals as the number of IDH events per 100 we whether parameters measured by and ultrafiltration volume were associated with IDH and whether this on time an HD session. We extracted RBV, and at the of and compared parameters between where IDH occurred and where it did not in that To for on a regression was used at time with RBV, or as the the or of IDH as a and as a This to RBV and for patients about to an IDH with were stable for at the minutes. To investigate associations between or HD and the time of we logistic regression to for on patients and the of between onset of IDH was used as the and treatment were and the were based on and analysis was for all variables, by (i) at all sessions comorbidities, dialysis and dialysate and (ii) from (i) and dialysate to serum which are only measured one session per We considered associations between time of IDH and both and cardiovascular mortality. We survival for patients prone to IDH and IDH and for early late IDH for chronic failure, and Patients were at the of the study on to a treatment or of the of Renal Research Institute of IDH was and using the median session interval for first IDH regression analyses were based on regression were as means intervals for the or of IDH in the minutes. and regression were as and of were considered analyses were using A and for for 1, Scholar The extracted data included patients with sessions from 21 dialysis The number of patients and sessions included in part of the analysis can be in Patients prone to IDH were more likely to be and have dialysis and likely to be an sessions where IDH occurred had treatment with and were to and systolic and blood pressure and pressure and treatment characteristics for the cohort and by whether the patient is prone to IDH for patient data or whether the session included an IDH for session of IDH of per access mm mm mm mm pressure, mm chronic blood HD, intradialytic peripheral peripheral vascular systolic blood ultrafiltration are number for and number for in a new chronic blood HD, intradialytic peripheral peripheral vascular systolic blood ultrafiltration are number for and number for our primary definition of IDH SBP <90 mm the median for first IDH in a session was to minutes. There was no in IDH incidence across session with a of to episodes per 100 Intradialytic RBV, and results are in based on whether IDH in the minutes or There were no significant in RBV and between where IDH is compared with where no 90 which RBV and are both notably preceding IDH. There was a significant reduction in and preceding IDH at all time no was for demographic factors, being prone to increasing and were all associated with IDH in treatment factors, and and SBP logistic regression for the of IDH in the first of a session compared with later in the per to serum chronic intradialytic peripheral peripheral vascular systolic blood analysis for all for all treatments for it all from and in a number of treatments to of these data in a new chronic intradialytic peripheral peripheral vascular systolic blood analysis for all for all treatments for it all from and in a number of treatments to of these data a median of there were of which were cardiovascular analysis and cardiovascular mortality for patients to have IDH early in a session analysis survival in patients prone to early IDH mortality cardiovascular mortality analysis of the association of IDH with both and cardiovascular chronic intradialytic in a new chronic intradialytic a definition mm of the incidence was all other definitions of of episodes per 100 the median did not change a reduction of at mm Hg from to the definition of IDH the total incidence of and the incidence of IDH in the early part of HD, with only and per 100 session intervals in the first and compared with and using our primary definition of IDH The median for first IDH by to to minutes. fluid as a of interventions to IDH incidence of IDH of total a of episodes per 100 and a median of 90 to minutes. We regression and survival analyses using a definition of nadir SBP <90 mm Hg and a decline in SBP mm which results to using the primary and and and We have that defined as SBP <90 mm throughout HD at a relatively stable This is on how IDH is the for of IDH definition in and clinical Furthermore, our results suggest that the of RBV and to IDH onset is on the time an HD session. we were to in clinical and treatment as well as survival between patients prone to IDH early and late in a session. Despite a that most IDH episodes the of a intradialytic hypotension to of Am Soc Nephrol. 2015; 26: PubMed Scopus Google Scholar there are little data on IDH and Santoro monitoring of patients, a time of IDH of minutes a P. Santoro A. Dialysis-induced hypotension: a fresh look at pathophysiology.Blood Purif. 1993; 11: 85-98Crossref PubMed Scopus (86) Google Scholar This is notably later we the study not have a definition of IDH and not whether it only the first IDH in any given session. Intradialytic blood pressure which are associated with have been A reduction in SBP during HD has been of a early decline across the first of the treatment and a with significant K. K. et of systolic blood pressure during the of dialysis and clinical factors associated with various blood pressure J 2011; Full Text Full Text PDF PubMed Scopus Google T.I. based on a of an using blood pressure during hemodialysis 2015; PubMed Scopus Google Scholar This be to the relatively incidence of IDH early in a session the rate of of fluid from the by ultrafiltration is central to the of IDH. our results no significant in the at and 90 minutes between sessions where IDH is and where it is not, was not notably at these time This to the other of fluid of the the changes in at the of which are associated with fluid and blood pressure A.T. Mc Causland F.R. Osmolality and blood pressure stability during hemodialysis.Semin Dial. 2017; 30: 509-517Crossref PubMed Scopus (15) Google Scholar The use of RBV for and of IDH is well but D. J. M. time for blood volume J. 2018; PubMed Scopus Google Scholar The RBV are with F. M. E. et of blood volume monitoring for fluid in hemodialysis Purif. 2013; PubMed Scopus Google et of fluid of using both analysis and blood volume PubMed Scopus (15) Google Scholar and the in SBP The aspect in these data is were significant throughout HD, in RBV preceding IDH are so small to be during the early period of a session. in the RBV is notably preceding an IDH intradialytic measurement is more has been shown to reduce with increasing C.W. venous oxygen a new for in haemodialysis PubMed Scopus Google H. L. A. et al.Association between intradialytic central venous oxygen saturation and ultrafiltration volume in chronic hemodialysis Dial Transplant. 2018; PubMed Google Scholar and to associate with L. H. A. et al.Intradialytic central venous oxygen saturation is associated with clinical outcomes in hemodialysis 2017; PubMed Scopus Google Scholar in and is of IDH E. C. L. et blood oxygen saturation association with dialysis hypotension Nephrol. 2016; 30: PubMed Scopus Google Scholar results that and but not are notably preceding an IDH This be by the that and related to can cardiac output and which is more of H. L. A. et al.Association between intradialytic central venous oxygen saturation and ultrafiltration volume in chronic hemodialysis Dial Transplant. 2018; PubMed Google A. Y. H. et al.Intradialytic is associated with intradialytic arterial oxygen Dial Transplant. 2018; PubMed Scopus Google Scholar These data to how RBV and are and to define outcomes to the evidence base for widespread Patients prone to IDH in were more likely to be and and have blood pressure, dialysis and which is with Usvyat L.A. T. et al.Intradialytic hypotension: of and with clinical Int. 18: PubMed Scopus Google Scholar factors associated with IDH per were associated with with the being and and which were associated with IDH in while being associated with IDH. is to have associations with outcomes in kidney K. C. J. et al.The in kidney how to it with 2017; Full Text Full Text PDF PubMed Scopus Google Scholar and this is likely to to the between and IDH. is to and but patients with to be to and fluid D. P. et of the monitor for fluid in with 2016; PubMed Scopus (6) Google Scholar studies that had no association with and were associated with M. Y. et al.Association of and intradialytic hypotension in hemodialysis Purif. PubMed Scopus Google J. et between measurement by analysis and intradialytic Nephrol. PubMed Scopus Google Scholar to the in as a for is to C. et al.Intradialytic hypotension and risk of cardiovascular J Am Soc Nephrol. PubMed Scopus (151) Google Scholar and J.E. the ultrafiltration the of session and J Am Soc Nephrol. 2013; PubMed Scopus Google is to and this has been shown to on the between and Y. et and mortality association with serum the and 2017; Full Text Full Text PDF PubMed Scopus Google Scholar and be factors in the of IDH. is in myocardial and have a in of blood pressure during et al.Effect of dialysate on intradialytic blood pressure in cardiac J Full Text Full Text PDF PubMed Scopus Google Scholar have increasing blood pressure but not associated with D. et of intradialytic hypotension with the of dialysate to and/or J Full Text PDF PubMed Scopus Google Scholar and that intradialytic blood pressure J. J. L. et during hemodialysis: use and clinical Int. Full Text Full Text PDF PubMed Scopus Google Scholar The risk of with our data be considered as of be related to patients being prone to IDH. This the association with IDH and the in both and in sessions where IDH occurred The association between and mortality is well M.M. Flythe J.E. ultrafiltration and outcomes hemodialysis patients: the evidence 2015; PubMed Scopus (15) Google Scholar but there are little data associations between and and data per is associated with of et treatment time and ultrafiltration in hemodialysis: associations with mortality in the Int. Full Text Full Text PDF PubMed Scopus Google Scholar We to be in patients prone to IDH and increasing to be associated with of IDH. This be related to of to was in or to the reduction of in patients. analysis and analysis suggest that IDH is associated with both and cardiovascular mortality. including chronic and which the to for fluid on be to IDH and the association with survival. the associations were for a number of Sensitivity analyses the of how IDH is defined for both and management of IDH. The of a reduction in SBP to a nadir reducing the on the the number of IDH early in a there was notable incidence in the first of dialysis in all definitions We all including survival using the definition of a and a SBP in an to reduce the of IDH episodes to chronic hypotension results were to this IDH is likely the of there is little in treatment. the associations with to prevent IDH have significant on is to the and interventions IDH early in but include the of changes in the early of dialysis blood and central blood volume dialysate and ultrafiltration and further of the early L. H. et al.Intradialytic in chronic hemodialysis Purif. 2016; PubMed Scopus Google Scholar and by this This is the first study to characterize the time of onset of IDH. is based on a cohort from the network of Renal Research Institute across the United States. We included all patients in these clinics during the study dialysis and data are all to US Renal data and antihypertensive data to be likely to data being given the as a response in the IDH per session for the definitions are to reported J.E. Xue H. Lynch K.E. et al.Association of mortality risk with various definitions of intradialytic hypotension.J Am Soc Nephrol. 2015; 26: 724-734Crossref PubMed Scopus (190) Google Scholar further for the of the data were not for all patients, but the use of is a based on patient with observational be Associations between variables, as HD prescriptions, and IDH are likely to include by We have a in the time of onset of IDH throughout a treatment which is associated with and variables, including survival. of time of IDH to IDH episodes and use of interventions, that a

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