- Title
- Individualized blood pressure targets and the incidence of new-onset acute kidney injury among critically ill patients with shock
- Creator
- Panwar, Rakshit
- Relation
- University of Newcastle Research Higher Degree Thesis
- Publisher Link
- http://dx.doi.org/10.25817/ZGFN-XM89
- Resource Type
- thesis
- Date
- 2021
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Each year over 10,000 Australians who are treated for shock in intensive care unit (ICU) develop acute kidney injury (AKI). According to some series, up to half of these patients could die before leaving hospital. The annual burden of death due to shock with AKI is nearly thrice that of the annual road toll. Development of AKI during shock is an independent predictor of mortality, and its attributable excess treatment cost in Australia exceeds $80 million annually. Strategies that may help prevent AKI or expedite recovery from AKI are much needed. Maintaining an adequate blood pressure (BP) is one of the fundamental tenets of management of shock, and therefore it may potentially have an impact on the development or progression of new-onset AKI. However, optimal BP targets that can minimize risk of AKI among individual patients are not that clear. In particular, there is paucity of data on the concept of relative hypotension, that is the BP deficit between a patient’s usual pre-illness resting BP and the achieved BP in ICU whilst on vasopressor support. The overarching goal of this research program is to test the hypothesis whether BP targets that are individualized and based on patients' usual pre-illness resting BP may have an association with or may have an impact on the incidence of new onset AKI or major adverse kidney events (MAKE) amongst critically ill patients with shock. As one of the first steps to address this goal, a conceptual scoping review (chapter 7) was conducted to synthesize current knowledge and lay down existing evidence for BP targets. The review discussed the physiological rationale for individualized BP targets that aim to minimize the degree of relative hypotension during vasopressor therapy. This review demonstrated the lack of quality evidence on this concept and indicated that untreated relative hypotension may be associated with adverse outcomes such as new AKI. Notably, at the time of this review, none of the contemporary standard resuscitation protocols specifically mentioned or recommended targeting an individual patient’s own pre-illness BP as a potential target for vasopressor therapy. The novel contribution of this review was to put a spotlight on this under-recognized concept, spark further discussion on the merits of treating relative hypotension, and advance the argument for further quality research. This program of research began with a preliminary single-center retrospective proof-of-concept study (chapter 8), which investigated the incidence of untreated relative hypotension in patients with shock during vasopressor therapy at a tertiary care academic ICU. Since both mean arterial BP (MAP) and central venous pressure (CVP) could impact on the net perfusion pressure for the vital organs, so the mean perfusion pressure (MPP= MAP−CVP) was considered a key hemodynamic variable in this study. The MPP achieved in ICU (achieved-MPP) was compared to the patients’ pre-illness resting BP (basal-MPP) and the time-weighted average MPP-deficit – i.e., the difference between basal-MPP and achieved-MPP – was derived as a measure of overall burden of relative hypotension. An a priori specified and preset protocol was followed to estimate basal-MPP. The novel aspect of this study was that the time-weighted average achieved-MPP and the magnitude of MPP-deficit in current practice during the vasopressor therapy for ICU patients with shock were comprehensively described for the first time. This study showed that the achieved-MPP among ICU patients with shock had no relationship to their basal-MPP, and BP targets were not usually individualized during management of shock among ICU patients. In this single center retrospective study, both the degree and the duration of MPP-deficit appeared to have an association with subsequent AKI. However, this was not high-quality evidence, and therefore these findings were considered as hypothesis-generating. These results emphasized the need to replicate this study in a broader clinical practice. Before embarking further, since a patient’s basal-MAP is considered a useful reference point for assessing degree of relative hypotension, it was also important to assess whether the study protocol for estimating basal MAP was reliable and valid. To answer this question, a study (chapter 9) was conducted to assess mean bias between the basal-MAP estimated using a preset protocol based on up to five recent pre-morbid clinic BP measurements (as used in this research program) and the basal-MAP measured with the nighttime ambulatory BP monitoring (ABPM), among a cohort of patients who recently underwent an ABPM test through the hospital service. This study showed that the protocol-estimated MAP values, on average, approximated the actual ABPM-measured MAP values, with an overall mean bias of less than 1 mmHg. This led to the conclusion that, where a recent ABPM is unavailable, a standardized protocol that is based on recent available clinic BP measurements can be used to estimate a patient’s basal MAP. To address the lack of any high-quality evidence or prospective multicenter studies exploring the relationship between relative hypotension and adverse kidney-related outcomes among critically ill patients with shock, a multicenter prospective cohort study (chapter 10) was conducted. This study enrolled 302 patients at seven tertiary Australian ICUs over a period of four years. The aim of this study was to assess the degree of BP-deficit in conventional practice during vasopressor-support among critically ill patients with shock, and to determine whether such BP-deficit during first five days of vasopressor therapy could have any relationship with the incidence of new significant AKI or MAKE within 14 days of vasopressor-initiation. In this multicenter prospective cohort study, among ICU patients with shock, a significant degree of relative hypotension was observed, perhaps subliminally accepted, during vasopressor support; and multivariable-adjusted analyses showed that the odds of developing new significant AKI and MAKE-14 increased significantly with increasing degree and duration of relative hypotension. These findings imply that a strategy that adjusts BP targets based on patients’ pre-illness basal BP may have a potential to improve outcomes among ICU patients with shock and need to be tested in future interventional trials. The next phase (chapter 11) of this research program would consist of interventional trials comparing standard care to a strategy of targeting patients' pre-illness BP during management of shock in ICU. A multicenter pilot randomized controlled trial (RCT) that will enroll 50 patients is underway. This RCT will investigate whether targeting patients' pre-illness BP during vasopressor support is a safe and efficacious strategy in reducing the incidence of new-onset AKI among vasopressor-treated patients with shock. This RCT will provide pivotal data on the effects of individualizing BP targets in ICU and may pave way for a definitive RCT in future.
- Subject
- shock; critically ill; relative hypotension; acute kidney injury; individualized; blood pressure targets; vasopressor therapy; intensive care unit; thesis by publication
- Identifier
- http://hdl.handle.net/1959.13/1434542
- Identifier
- uon:39453
- Rights
- Copyright 2021 Rakshit Panwar
- Language
- eng
- Full Text
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| View Details Download | ATTACHMENT01 | Thesis | 23 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 607 KB | Adobe Acrobat PDF | View Details Download |