Current practice of diagnosis and management of acute kidney injury in intensive care unit in resource limited settings

Accepted Manuscript Current practice of diagnosis and management of acute kidney injury in intensive care unit in resource limited settings

Nattachai Srisawat, Nattaya Sintawichai, Win Kulvichit, Nuttha Lumlertgul, Patita Sitticharoenchai, Nicha Thamrongsat, Sadudee Peerapornratana PII: DOI: Reference:

S0883-9441(18)30009-1 doi:10.1016/j.jcrc.2018.04.007 YJCRC 52907

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ACCEPTED MANUSCRIPT Current practice of diagnosis and management of acute kidney injury in intensive care unit in resource limited settings

Nattachai Srisawata,b, Nattaya Sintawichaia, Win Kulvichita,b, Nuttha Lumlertgula, Patita

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Sitticharoenchaia, Nicha Thamrongsata, Sadudee Peerapornratanaa,b

a

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Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn

University, and King Chulalongkorn Memorial Hospital, Bangkok, Thailand b

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Center for Critical Care Nephrology, The CRISMA Center, Department of Critical Care

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Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States

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Keywords: acute kidney injury, resource limited settings, Southeast Asia, practice, ICU Short running head: Current AKI management in Thailand ICU

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Nattachai Srisawat, M.D., M.Sc.

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Corresponding author:

Division of Nephrology, Department of Medicine,

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Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Bangkok, Thailand

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E-mail: [email protected] Competing interests

The authors declare that they have no competing interests.

ACCEPTED MANUSCRIPT Abstract Purpose: In a resource limited settings, there is sparse information about the management of acute kidney injury (AKI) based on systemic data collection. This survey aimed to described the current management of AKI in intensive care units (ICUs) across Thailand.

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Materials and methods: Questionnaires were distributed to 160 physicians involved in the

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intensive care between January and December 2014 across Thailand. Distribution was done through an via online survey platform or telephone interview.

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Results: The response rate was 80.6% (129 physicians). AKI diagnosis was mostly made

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by using KDIGO criteria (36.7%). A common diagnostic investigation of AKI was urinalysis (86%). Nephrologists had a major role (86.4%) in deciding the initiation and selection of

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renal replacement therapy (RRT) modality. Intermittent hemodialysis is the preferable mode of RRT (72.0.0%), followed by continuous renal replacement therapy (CRRT, 12%),

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sustained low efficiency dialysis (10.0%) and peritoneal dialysis (6.0%). Catheter insertion

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was predominantly performed by nephrologist (51.1%) with ultrasound guidance. The right internal jugular vein was the most common site of insertion (70.4%). The most common

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indication for CRRT was hemodynamic instability. Conclusions: Amid increasing concern of AKI in the ICU, our study provides the insight

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into the management of AKI in resource limited settings.

ACCEPTED MANUSCRIPT 1. Introduction Acute kidney injury (AKI) is an important and common problem in the intensive care unit (ICU). Worldwide prevalence of AKI in ICU ranges from 20%-70%, with a rate of renal replacement therapy (RRT) of 10% [1-3]. Regardless of clinical setting, AKI has been linked to increased morbidity and mortality.

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After the introduction of Risk, Injury, Failure, Loss and End (RIFLE) criteria [4, 5],

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Acute Kidney Injury Network (AKIN) criteria [6] and the latest, Kidney Disease Improving Global Outcomes (KDIGO) criteria [7], the definition and staging of AKI has become more

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standardized. Even though, these criteria are widely adopted in resource sufficient

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settings. Little is known about their use in resource limited settings [8]. Furthermore, there is still no adequate systemic data collection on which diagnostic

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investigations were devised in this specific setting. AKI greatly increases cost of medical care, therefore, gaining information regarding the diagnostic methods most commonly

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used will help provide a practical insight to better understand our practice of AKI

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management in resource limited settings.

Optimal management of AKI, especially RRT initiation in patients with advanced

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AKI stages will much decrease morbidity and mortality [9, 10]. Many national surveys of current practice of RRT management were previously conducted in many countries such

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as Australia and New Zealand [11],UK [12], Europe [13], Japan [14] and Malaysia [15]. However, there are a few reports from resource limited settings. This survey aimed to systematically collect data to reflect the current clinical management of AKI in hospitals across Thailand.

ACCEPTED MANUSCRIPT 2. Materials and methods 2.1. Survey and participants To conduct this prospective study, we identified roughly 400 physicians who participated in the annual Thai nephrology conference and/or who were members of the Thai Nephrology Society between January and December 2014. We randomly selected

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160 physicians who were involved in ICU practices and invited them to participate in our

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study by answering a questionnaire administered through online Survey Monkey or telephone interview.

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2.2. Survey design

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The 48 questions in the survey were mainly divided into the diagnosis of AKI and treatment modalities. This study specifically addressed the issue of RRT management.

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Survey questions included both closed-ended and open-ended questions. Subsequently, the data from individual respondents was collected and analyzed.

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2.3. Statistical analysis

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Statistical analyses were performed using SAS edition 3.6 (Basic Edition), Cary, NC, USA. The categorical data were summarized as percentage and continuous variables

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were summarized as median (25th, 75th quartiles).

ACCEPTED MANUSCRIPT 3. Results The survey was distributed to 160 physicians involved in the critical care practices. One hundred and twenty-nine across 82 hospitals responded. We achieved a response rate 80.6% and cover 40% of Thailand hospitals with an ICU facility. Physicians were composed of nephrologists (69.0%), internists (22.0%), intensivists (7.8%), general

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practitioners (0.8%), and others (6.3%). The median age of survey participants was 36

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(IQR 33-42) years. All level of hospitals were included in our survey: University hospitals (33.9%), regional hospitals (37.1%), and provincial hospitals (29.0%). We incorporated

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both public hospitals (82.8%) and private hospitals (17.2%). We also characterized level of

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hospital by the number of care-bed; up to 150 beds (15.6%), 151-500 beds (28.9%) and more than 500 beds (55.5%).

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3.1. AKI diagnosis

AKI diagnosis was defined by standard criteria 90.8% of the time. KDIGO was the

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most commonly used criteria, followed by AKIN, and RIFLE (Table 1). Furthermore, basic

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laboratory usage was also assessed. Urinalysis appeared to be the most frequently used test for AKI diagnosis. Regarding to urine indices, Fractional excretion (FE) of sodium was

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the most common prescription test. For radiologic investigation during admission, most of the participants order KUB (kidney, ureter, and bladder) ultrasound. The attitude of

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participating physicians towards novel AKI biomarkers showed that 81.4% of them agreed with their benefit over their risk. The perceived utility of novel AKI biomarkers was their help diagnosing AKI, followed by prognosticate (55.8%), decision of RRT initiation, and triage of AKI patients (Table1). 3.2. RRT practice in Thailand In Thailand, the current decision making towards initiation and selection of RRT modality mostly depended on nephrologists, followed by intensivists, general practitioners,

ACCEPTED MANUSCRIPT and internists, respectively (Figure 1). In well-equipped ICUs with all available modes of RRT, intermittent hemodialysis (IHD) was the mode of choice, followed by continuous RRT (CRRT), sustained low efficiency dialysis (SLED), and peritoneal dialysis (PD) (Figure 2). However, all modalities of RRT are not currently available in every ICU. Most ICUs had IHD, followed by SLED, PD and CRRT (Table 2).

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Intermittent hemodialysis practice

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Physicians who prescribed IHD were mostly nephrologists (95.2%), followed by internists (11.2%), intensivists (8%) and general practitioners (2.4%). The frequency of

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hemodialysis was mostly 3 times/week, followed by 2 times/week, and more than 3

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times/week depending on the clinical situation (Figure 3). The main water purification system was portable reverse osmosis (76.7%), compared to the water treatment system

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(23.3%).

Continuous renal replacement therapies (CRRT) practice

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CRRT was predominately prescribed by nephrologists (97.7%), followed by

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intensivists (10.2%), internists (3.4%), general practitioners (1.1%), and surgeons (1.1%). During CRRT, ICU nurse played an important role in maintaining the circuit (84.9%).

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The types of available CRRT machines in the ICU were integrated machines (55.3%), followed by manual machines (18.8%). About 18.82% of respondents reported that their

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units had both types of the machines. The mean of integrated machines in ICU was 2.3 machines/unit. Among CRRT, continuous venovenous hemofiltration (CVVH) was the most frequent, followed by continuous venovenous hemodiafiltration (CVVHDF), and continuous venovenous hemodialysis (CVVHD) (Figure 4). Among the many reasons CRRT was performed in the ICU, the most important one was cardiovascular instability (96.7%), followed by control of fluid balance (26.7%), brain

ACCEPTED MANUSCRIPT edema (21.1%), and the high efficacy (13.3%). Dosage of CRRT varied with 20-25 mL/kg/hr in the majority and 30-35 mL/hr in the minority. Anticoagulation was an essential component of all blood-based therapies including CRRT. In our findings, unfractionated heparin was the first-line anticoagulant for CRRT reported about 63.22%. No one used citrate as anticoagulant and 32.0% reported no

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usage of any kind of anticoagulant in the system.

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In both IHD and CRRT, the double lumen dialysis catheter was predominantly inserted by nephrologists (92.8%). Regarding techniques for vascular access, the right

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internal jugular vein was the most frequented site (70.4%), followed by femoral vein

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(29.6%). The left internal jugular and subclavian vein were not a preferable site for catheter insertion. Ultrasound guidance catheter insertion was used as followed: almost all

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the time (21.8%). sometimes (53.3%), while 25.0% of respondents reported that they performed catheter insertion without ultrasound guidance.

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Peritoneal dialysis practice

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In PD, nephrologists predominantly initiated and prescribed dialysate solution (95.2%), followed by internists (16.3%), general practitioners (16.3%), intensivists (3.1%)

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and surgeons (1%). The main reason for choosing PD was the 24 hour availability (36.7%) , followed by unavailability of hemodialysis (9.2%), low cost (7.1%) and high efficacy

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(3.1%). In terms of technical procedure, peritoneal catheter insertion was performed by surgeons (72.2%), nephrologists (43.3%), internists (20.6%), general practitioners (7.2%) and intensivists (4.1%). In each cycle, dialysate fluid removal and replacement was done by critical care nurse (93.4%) and hemodialysis unit nurses (18.4%).

ACCEPTED MANUSCRIPT 4. Discussion Interestingly, the survey practice of AKI in resource limited countries may reveal different socioeconomic, environmental, and processes of care than in resource sufficient countries and may help to identify the important barriers. This, in turn, will help in the improvement AKI management which ultimately lead to better clinical outcomes. Our

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survey achieved in high response rate. Diagnosis of AKI was mostly defined by KDIGO

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criteria, and AKI assessment was mostly done through urinalysis (86.0%). In our study nephrologists play many major roles in the management of AKI especially in the initiation

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and mode selection of RRT which differs from a previous national survey that most of

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these decisions were made by intensivists [6]. IHD was the first-choice RRT modality used to treat AKI in critically ill patients, while other RRT modalities (CRRT and PD) were used

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less frequently. Among CRRT, CVVH was the most commonly used technique. The steps taken to diagnose AKI are in line with current practice. In resource

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limited settings, physicians tend to select only necessary investigations to optimize cost

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and treatment benefit for patients. Urinalysis and urine microscopy have always been crucial laboratory tests needed for identifying the etiology of AKI and most importantly, they

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are simple and inexpensive. Even though other blood and urine biochemistry test (ie. FE sodium, FE uric acid, and urine osmolarity), have been shown to correlate with the severity

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of AKI [16, 17]. They are more expensive and sometimes not available in rural hospitals. The usefulness of urine biochemistry has been questioned in the setting of sepsis and prior diuretic exposure [18, 19]. Moreover, the role of such tests without serial measurement is often limited and unclear [20]. Renal ultrasound is useful in differentiating preexisting CKD from AKI, especially in patients without any data on baseline renal function, and to diagnose urinary tract obstruction. Therefore, it highly depends on clinical context which patient needs renal ultrasound.

ACCEPTED MANUSCRIPT Overall, RRT practices in Thailand were quite different to those observed in resource sufficient countries. We have summarized the available RRT survey practice in Table 3. In our survey, IHD is a first preferable mode of RRT which contrasts to previous studies where CRRT was the preferable mode (Table 3). This notice difference could be related to the lower cost of IHD. The results from The Beginning and Ending Supportive

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Therapy for the Kidney (BEST Kidney) [21] study conducted among 53 centers from 23

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countries, showed that range of costs were greater with CRRT, starting from 3,629.8 USD/day with CRRT to 378.6 USD/day with IHD. The median difference in cost between

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CRRT and IHD was 289.60 USD (IQR 116.8-830.8) per day. In Thailand, the average cost

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of CRRT is 1,000 USD/day while the cost of IHD is only 100 USD/day. Moreover, evidence from existing studies does not support an outcome advantage of one modality versus the

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other, albeit limited. Several randomized, clinical trials have compared the outcomes of IHD and CRRT in critically ill patients with AKI showed no convincing evidence to support

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superiority of CRRT over IHD [22-25]. In Thailand, in ICUs where all RRT modalities were

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available, IHD was still the preferable RRT modality. Our data confirmed the use of PD as a choice of RRT in resource limited countries especially due to limited hours of IHD

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facilities during the night time. The rate of PD selected as a first choice for RRT is similar to that from developed countries and its use is lower than other modalities [26].

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IHD was frequently prescribed 3 times/week in most ICUs. Nevertheless, evidence does not support a need to routinely provide dialysis treatment more frequently than every other day as long as KT/V urea at least 3.9/week can be achieved [7, 25]. It is noteworthy to mention that the water purification system for IHD, was mainly driven by portable reverse osmosis system which might affect to the quality of dialysate fluid and patient outcomes. This is an area where there is room to improve the quality of care for IHD.

ACCEPTED MANUSCRIPT In our survey, CVVH, is the preferable mode of CRRT, and from current evidence comparing different modalities of CRRT, there is no evidence that CVVH (convection) is different than CVVHDF (convection plus diffusion) in terms of patient outcomes or renal outcomes [7]. Most respondents reported using integrated CRRT machines, which are sophisticated and expensive machine and only provided in well-equipped ICUs. Current

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studies of efficacy of manual or separated system CRRT show that they use simple and

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safe CRRT techniques at much lower cost than integrated systems [27]. Separated or manual systems may be beneficial in the units with limited resources. The preferred choice

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of dialysis dose is 20-25 ml/kg/dose which is in line with current evidence suggesting no

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additional benefit in using effluent rate in excess of 20 ml/kg/hr [25]. There are several strengths in our study. First, our study is the first survey to

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systematically collect data about AKI management in resource limited countries. Secondly, our finding these data are crucial in establishing baseline data of AKI management in

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resource limited countries. Thirdly, our results are crucial in informing how to improve

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quality of care, standardize practice, and reimburse healthcare budgets. Lastly, this data will provide a framework for designating AKI interventions applicable to resource limited

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countries.

We acknowledged that our survey has a number of limitations. First, most

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respondents work in provincial, and regional hospitals, so our findings might not be generalizable to primary care units or hospitals in rural areas. However, all respondents are physicians who manage AKI in major ICUs across Thailand and their responses are likely to represent current practice. Secondly, our study is subject to recall bias. Lastly, the data generated from our survey is qualitative. However, this may lead to more quantitative studies.

ACCEPTED MANUSCRIPT 5. Conclusions With increasing concern about current practice of AKI management in ICU, our study showed both the similarities and differences of AKI practice between resource limited settings and resource sufficient settings. It is noteworthy to emphasize that in Thailand, nephrologists play a major role in AKI management and that IHD is a main RRT

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modality. Our survey results may help provide insights into the current standard of care of

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AKI in resource limited settings and ultimately aims to guide the future improvements in

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AKI management.

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Competing interests

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The authors declare that they have no competing interests.

Acknowledgements

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This study is a part of a project supported and funded by the Excellence Center for

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Critical Care Nephrology, King Chulalongkorn Memorial Hospital, Thai Red Cross. We thank the staff, fellows, nurses and research co-ordinators at the Excellence Center for

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Critical Care Nephrology.

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ACCEPTED MANUSCRIPT Table 1. AKI Diagnostic methods used in ICU across Thailand Number of respondents

Percent %

Criteria (N = 119) RIFLE

31

26.1

-

AKIN

33

27.7

-

KDIGO

44

37.0

-

Not use any criteria

11

9.2

Urine microscopy (N = 127)

48

Urine sodium (N = 129)

55

Fractional excretion

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111

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Urinalysis (N = 129)

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-

86.0 37.8 42.6

Sodium (N = 129)

78

-

Urea (N = 129)

44

-

Uric acid (N =129)

24

18.6

29

22.5

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-

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Urine osmolarity (N = 129) Renal ultrasound (N = 127) All cases

-

Some cases

-

Never

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-

60.5 34.1

62

48.8

65

51.2

0

0

ACCEPTED MANUSCRIPT Table 2. Available modality of RRT in ICU across Thailand Mode of RRT

Available

In ICUs

Not available

Percent

Number of

respondents

%

respondents

CRRT (N = 127)

90

70.9

37

29.1

IHD (N = 127)

121

95.3

6

4.7

SLED (N = 127)

105

82.7

22

17.3

PD (N = 126)

100

79.4

26

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Percent %

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Number of

20.6

ACCEPTED MANUSCRIPT Table 3. Comparison of national or multinational survey of AKI practice (after 2005) Author

Year Country Setting No. of respondents Levels of hospital

AKI diagnosis

Initial mode of RRT

Ricci et al. [28]

Overberger et al. [29]

Basso et al. [30]

Legrand et al. [13]

Iwagami et al. [14]

Jamal et al.* [15]

Raina et al. (pediatric) [31]

Clark et al.* [32]

Our study*

2006 International ICU 560

2007 USA Hospital 130

2010 International ICU 440

2013 International ICU 272

2016 Malaysia ICU 19

2017 International Hospital 223

2017 China Hospital 200

2017 Thailand ICU 129

Academic hospitals (43%) Community of city hospitals (51%) NA (6%)

Veteran Affairs (VA) medical centers (64.6%) Non-VA medical centers (35.4%) NA

NA

Academic hospitals (76.5%) Nonuniversity hospitals (23.5%)

2015 Japan ICU NA (from national database) Academic hospitals (24.933.5%)

NA

Class 3 (70%) Class 2 a (30%)

NA

NA

Infants Developing countries: PD (68.5%) Developed Countries: HD (72%) CRRT (24%)

CRRT (63.9%) IHD (24.8%) PD (5.2%)

Academic centers (70.9%) Provincial hospitals (21.8%) District hospitals (7.3%) RIFLE (25.8%) AKIN (27.5%) KDIGO (36.7%) IHD (72%) CRRT (12%) SLED (10%) PD (6%)

RIFLE (16%) Oliguria (24%) Combination (5%) CRRT (91%) IHD (69%) SLED (24%)

A

NA

CRRT (86%) IHD (65%) SLED (28%) PD (30%)

CRRT (37.1%) IHD (+SLED) (10.6%) Either (51.8%)

T P E

C C

IHD (57%) CRRT (35.7%) SLED (7.3%)

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U N

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RIFLE (55%) Oliguria (28%) Creatinine (10%)

I R

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Public hospitals (89.5%) University hospitals (10.5%)

T P

NA

CRRT (79.6%) IHD (20.4%)

NA

CRRT (79%) IHD (15.7%) SLED (5.3%)

ACCEPTED MANUSCRIPT Decision makers of RRT initiation

Nephrologists (52%) Intensivist (38%)

NA

Nephrologist s (61%) Intensivists (39%)

Modality of RRT (CRRT)

HDF (63.6%) HF-pre (53.6%) HF-post (28.9%) HF-pre+post (21.8%) HD (19.1%) UFH (66%) LMWH (20.2%) Regional heparin (6.3%) RCA (10.5%) Prostacyclin (12.5%)

NA

HF (69%) HDF (48%) HD (39%)

Anticoagulants

NA

UFH (80%) LMWH (20%) RCA (20%)

Intensivists (83.8%) Nephrologist s (7.4%) Intensivists with background in Nephrology (8.8%) HDF (50.9%) HF (40.6%) HF (9%)

T P E

Intensivist s (42%) Nephrolog ists (32%) Either (26%)

NA

HF (72%) HDF (56%) HD (27.8%)

NA

M

Developing countries: Adult nephrologist s (64.6%) Pediatric nephrologist s (35.4%)

NA

Nephrologist s (50%) Intensivists (50%)

Nephrologist s (86.4%) Intensivists (4.8%) General physicians (4.8%) Internists (4%)

Developing countries: HD (43.7%) HF (12.5%) HDF (12.5%)

HF (42%) HDF (35%) HD (23%)

HF (84.9%) HDF (10.5%) HD (4.7%)

Developing countries: Heparin (35.4%) Citrate (10.4%) No anticoagulan t (8.3%)

Heparinbased (65%) RCA (25%) No anticoagulant (10%)

UFH (63.2%) LMWH (3.5%) No anticoagulan t (32%) Citrate (0%)

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*Majority of participants from developing countries a In China, Class 2 hospitals have 100-500 beds; Class 3 hospitals have >500 beds. Abbreviation: USA, United States of America; ICU, Intensive care unit; NA, not available; AKI, acute kidney injury; RIFLE, risk, injury failure, loss, and end stage (RIFLE) classification; AKIN, acute kidney injury network (AKIN) classification; KDIGO, the Kidney Disease: Improving Global Outcomes (KDIGO) criteria; CRRT, continuous renal replacement therapy; IHD, intermittent hemodialysis; SLED, slow low-efficiency dialysis; PD, peritoneal dialysis; RRT, renal replacement therapy; HDF, hemodiafiltration; HF, hemofiltration; HD, hemodialysis; UFH, unfractionated heparin; LMWH, low molecular weight heparin; RCA, regional citrate anticoagulant

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Figure legends Figure 1. Initiation and mode selection of RRT Figure 2. Mode of RRT selected in ICUs Figure 3. Frequency of hemodialysis

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Figure 4. Mode of CRRT prescribed in ICU

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Highlight The largest survey study for AKI practice in ASIAN and resource limited settings Nephrologists play major role on AKI management and RRT initiation Intermittent hemodialysis is the preferred mode of RRT over continuous RRT and peritoneal dialysis

Figure 1

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Figure 4