RENAL AND HEPATIC DOSE ADJUSTMENT IN INTENSIVE CARE UNIT

PROJECT PRESENTATION

CLINICAL GUIDE INSTITUTIONAL GUIDE

Dr. DEVACHANDRAN.J MBBS;MD;FRCA;EDIC;MSC; Dr. ASWATHI ELISABETH PHILIP, PHARM D
Dr. KAMAKSHI MEMORIAL HOSPITAL ASSISTANT PROFESSOR
PALLIKARANI, CHENNAI. DEPARTMENT OF PHARMACY PRACTICE
K.K. COLLEGE OF PHARMACY

Submitted by
ASHIGA.C.M (381810205)
HEPHZIBAH ROXANE.S(381810208)
SASIDHARAN G(381810214)
YASHMI AGWINA XAVIER (381810217)
INTRODUCTION
• The kidneys have important physiological functions and play a major role in the excretion of drugs,
hormones, and xenobiotics. The liver plays a central role in metabolizing most drugs, which usually require
biotransformation for pharmacologic activity or excretion.
• Both the organs kidney and the liver are vital in maintaining the normal drug pharmacokinetics. In ICU
patients the physiological functions of kidney and liver is depressed therefore pharmacokinetic alterations
occurs in drugs metabolism and excretion and appropriate dose of any drug should be selected on the basis of
renal and liver function tests.
• Kidney function is assessed by a variety of tests and procedures that can be done to evaluate how well
kidneys are functioning. These tests are done on urine as well as blood samples. Many conditions can affect
the ability of the kidneys to carry out their vital function. The extent of loss of renal function is judged by
calculating creatinine clearance which is a useful measure of glomerular filtration rate. According to
reduction in creatinine clearance value the patients are categorized into mild, moderate and severe renal
impairment.
• The altered response to drugs in liver disease could be due the decreased metabolizing capacity of
hepatocytes, impaired biliary elimination, impaired hepatic blood flow leading to an increase in
bioavailability caused by a reduction in first pass metabolism and decreased protein binding.
RENAL CLEARANCE: The glomerular filtration rate was estimated based on creatinine clearance from serum creatinine
(SCr) using the Cockcroft Gault equation as shown below for men and women respectively:

• Male: CrCL (ml/min) = [(140-age) ×weight(kg)][Scr(mg/dl) ×72]

• Female: CrCL (ml/min) = [(140-age) ×weight(kg)×0.85][Scr(mg/dl) ×72]

HEPATIC CLEARENCE: Hepatic clearance was estimated by using Child Pugh score. Their original scoring system
used six clinical and laboratory criteria to categorize patients: serum bilirubin, serum albumin, ascites, neurological disorder,
prothrombin time and INR.

PARAMETERS SCORE 1 SCORE 2 SCORE 3

Encephalopathy none Grade 1 and 2 Grade 3 and 4
Ascites None slight Moderate
bilirubin < 2mg/ml 2-3mg/ml >3mg/ml
Albumin >3.5mg/ml 2.8-3.5 mg/ml <2.8mg/ml
Prothrombin <4 sec 4-6 sec >6 sec
INR <1.7 1.7-2.2 >2.2

The severity is classified as ( Inference )

 CHILD-PUGH A: 5-6 POINTS ( MORTALITY 10 %)
 CHILD- PUGH B: 7-9 POINTS ( MORTALITY 30%)
 CHILD-PUGH C: 10-15 POINTS ( MORTALITY 70-80%)
LITERATURE REVIEW
Getachew, et al.,(2015) conducted a study on drug dosage adjustment Abdulrahman M, et., (2011) conducted a study on Evaluation of applying
in hospitalised patients with renal impairment at Tikur Anbessa drug dose adjustment by physicians in patients with renal impairment. This
specialized hospital, Addis Ababa, Ethiopia. This prospective cross retrospective chart review was aimed to determine whether appropriate dose
sectional study was aimed to assess whether appropriate dosage adjustment was taken into account or not by the physicians when prescribing
adjustments were made in hospitalized patients with renal impairment. drugs in patients with renal impairment. The study included 98 adult in-
All patients with creatinine clearance ≤59 ml/min admitted to hospital patients, diagnosed with renal impairment based on clinical evaluation and
between April and July, 2013 were included in the analysis. Data laboratory data, in King Abdulaziz University Hospital (KAUH), Jeddah,
regarding serum creatinine level, age, sex and prescribed drugs and Saudi Arabia, who were admitted to the hospital from September 2005 to
their dosage was collected from the patients' medical records. Serum January 2011. Data of the patients were noted and recorded including
creatinine level ≥1.2 mg/dL was used as a cutoff point in pre-selection baseline demographics, clinical data, laboratory data, renal state, treatment
of patients. The estimated creatinine clearance was calculated using data and medications. The initial number of the patients was reduced to 80
the Cockcroft- Gault (CG) equation. Guideline for Drug prescribing in where a total of 502 drugs were investigated in the present study with an
renal failure provided by the American College of Physicians was average of six drugs per patient. Of these 502 studied drugs, 196 (39%)
used as the standard for dose adjustment. The study concluded the required dose adjustment where 92 (46.9%) were adjusted and 104 (53.1%)
nine percent (73/810) of medical admissions were found to have renal were not adjusted. It was found also that most of the drugs requiring dose
impairment (CrCl ≤ 59 ml/min). There were 372 prescription entries adjustment were antibiotics (39.8%).
for 73 patients with renal impairment. Dose adjustment was required
in 31 % (115/372) of prescription entries and fifty eight (51 %)
prescription entries requiring dose adjustment were found to be
inappropriate. Of 73 patients, 54 patients received ≥1 drug that
required dose adjustment. Fifteen (28 %) patients had all of their drugs
appropriately adjusted while twenty two (41 %) patients had some
drugs appropriately adjusted, and seventeen (31 %) of patients had no
drugs appropriately adjusted. No patients were documented to have
received dialysis.
LITRATURE REVIEW:

Manjula Devi A.S,et al.,(2016) conducted a study on dosage Mequanent Kassa Birarra, et al., (2012) conducted a study on drug
adjustments of potentially hepatotoxic medications in patients with liver dose adjustment in patients with renal impairment attending a
dysfunction. This is prospective descriptive study was carried out in the specialized referral hospital, Northwest Ethiopia. This prospective cross-
General medicine department of a 700 bedded multispecialty tertiary sectional study was aimed at investigating drug dose adjustment in renal
care teaching hospital for a period of 6 months (March – August 2014). impaired patients attending a specialized hospital. At the medical ward in
Patients admitted to the general medicine department, having at least University of Gondar comprehensive specialized hospital from March to
one elevated value of basic liver function tests, receiving at least one May 2018. During the study period, a total of 2100 patients were
pharmacologically active drug and willing to participate were included admitted to the general medical wards. They located and assessed 210
in the study. The degree of hepatic impairment was calculated using patient files, of which 189 patient files had complete notes. Based on our
Child-Pugh classification which incorporates five variables to assess the inclusion criteria, 105 patients had Crcl of ≥ 59 ml per min per 1.73 m 2.
severity of liver disease total bilirubin, serum albumin, prothrombin Therefore, 84 patients fulfilled their inclusion criteria and were included
time, the presence of encephalopathy and the presence of ascites. The in the final analysis. The study concluded that the mean age of study
dose of all drugs with potential hepatotoxicity was evaluated using the participants was 57 years with 57.1% male and 42.9% female. The
published drug dosing guidelines and the dosing interval was increased highest number of renal impaired patients was in stage three 56(66.7%).
or the total dose was reduced when necessary. 429 drugs in 50 patients The mean creatinine clearance (Crcl) was 41.8 ml/min, and the mean
were evaluated, of which, most of the drugs requiring dose adjustment serum creatinine (Scr) value of 2.63 mg/dl. More than two third (76.2%)
were antihypertensives followed by antidiabetics. Major type of error of the study participants had comorbidities. 84 patients with 257
identified was underdosing followed by overdosing and prescription entries were included in the study. Of which 75 prescription
contraindications. About 27.58% of the drugs were to be avoided in entries needed drug dose adjustment. The overall rate of inappropriate
hepatic impairment as per the available evidences. Drug dosing dose adjustment was 42.6% (32/75). Inappropriate dose adjustment was
evaluation and concurrent feedback mechanism by the pharmacist can more common with vancomycin (14.3%) and ciprofloxacin (6%).
improve drug safety in patients with hepatic impairment.
NEED FOR THE STUDY
• To evaluate the dose adjustment among hospitalized patients which will prevent poor therapeutic outcome
and toxicity resulting from dosing errors in patients with renal and hepatic impairment.
AIM & OBJECTIVE:

AIM:
To study and analyze dose adjustment among patients with renal and hepatic impairment in tensive care unit

OBJECTIVE:
 To study the drug dose calculation and adjustment in renal and hepatic impairment in intensive care unit.
 To observe the dose calculations based on the creatinine clearance and Child Pugh Score.
 To identify the class of drug that require frequent dose adjustment and continuous monitoring.
METHODOLOGY
This study was approved by Institutional Ethical Committee of Dr. Kamakshi Memorial Hospitals. Ethical committee
number: IEC-CS 23/BC-060/2023

STUDY DESIGN: A Prospective Interventional study

STUDY SITE: The study will be carried out in the AICU of Dr. Kamakshi Memorial Hospital, Chennai 600100.
STUDY PERIOD: The study was carried out for the 6 months.
STUDY POPULATION: 109 patients
POPULATION SELECTION:
INCLUSION CRITERIA EXCLUSION CRITERIA
Age above 18years of either gender. Age below 18years.
Patients with renal and hepatic failure. Pregnant and lactating women.
Patients admitted to intensive care.
PLAN OF STUDY:
RESULT & DISCUSSION
GENDER WISE DISTRIBUTION AMONG THE STUDY POPULATION

Out of 109 patients, 8(7.33%) male patients and no female patients had hepatic impairment. And 59(54.12%)
male patients 42(38.53%) female patients had renal impairment. In this study, the Male population was larger
than the Female population.
70
IMPAIRMENT MALE PERCENTAGE FEMALE PERCENTAGE
60
59
50
Hepatic 8 7.33% 0 0%

number of patients
40 42

30
Renal 59 54.12% 42 38.5%
20

10
Total 67 61.5% 42 38.5% 8
0
0 hepatic renal
Impairment

female male
AGE WISE DISTRIBUTION AMONG STUDY POPULATION
Among 109 patients, no hepatic and 3(2.75%) renal impairment patients were less than 45 years of age. 3(2.75) hepatic and 20(18.34%) renal
impairment patients were between the age of 46 and 60. 4(3.66%) hepatic and 58(53.21%) renal impairment patients were between the age of 61
and 75. 1(0.91%) hepatic and 18(16.51%) renal impairment patients were between the age of 76 and 90. No hepatic and 4(3.66%) renal patients
were above the age of 90.

60
AGE HEPATIC PERCENTAGE RENAL PERCENTAGE
50
Less than 45 0 0 3 2.75%

Number of patients
40
46 to 60 3 2.75% 20 18.34%
30
61 to 75 4 3.66% 58 53.21%
20
76 to 90 1 0.91% 18 16.51%
10
>90 0 0 4 3.66%
0
less than 45 46 to 60 61 to 75 75 to 90 >90
Age

hepatic renal
 TYPE OF IMPAIRMENT AMONG STUDY POPULATION:
Out of 109 patients, 101(93%) patients had renal impairment, and 8(7%) patients had hepatic impairment.

7%

TYPES OF NO. OF PATIENTS PERCENTAGE (%)

IMPAIRMENT
Renal 101 93% 93%

Hepatic 8 7%

RENAL HEPATIC
DOSE ADJUSTMENT OF RENAL AND HEPATIC IMPAIRMENT AMONG THE STUDY POPULATION

Out of 109 patients, 23(21%) patients required renal dose adjustments, 1(1%) patient required hepatic dose adjustment and remaining 85(78%)
patients required no dose adjustments RENAL HEPATIC NO ADJUSTMENT

21%

ADJUSTMENT NUMBER OF PERCENTAGE

PATIENTS
1%
Renal 23 21%

Hepatic 1 1%

No adjustment 85 78%
78%
DISTRIBUTION IN STAGES OF RENAL IMPAIRMENT AMONG STUDY POPULATION:
Among 101 renal impairment patients, no patients had stage 1, 4(4%) patients had stage 2, 34(33%) patients had stage 3, 33(33%) patients
had stage 4 and 30(33%) patients had stage 5 renal failure.
Stage II
Stage 4%
V
STAGES NO. OF PATIENTS PERCENTAGE (%) 30% Stage
III
34%
Stage I 0 0%
Stage II 4 4%
Stage III 34 33%
Stage IV 33 33%
Stage V 30 30%
Stage IV
33%

NUMBER OF RENAL DOSE ADJUSTMENT DONE DURING THE STUDY PERIOD:

Among 101 renal impairment patients 23(23%) patients required dose adjustments and remaining 78(77%) patients required no dose
adjustments.

23%

NUMBER OF DRUGS PERCENTAGE

Adjustment 23 23%
No adjustment 78 77% 77%

adjustment no adjustment
DISTRIBUTION IN STAGES OF HEPATIC IMPAIRMENT AMONG STUDY POPULATION BASED ON CHILD-PUGH SCORE:
Among 8 hepatic impairment patients, no patients had Child-Pugh A, 2(25%) patients had Child-Pugh B and 6(75%) patients had Child-Pugh C.

CHILD-PUGH SCORE NO. OF PATIENTS PERCENTAGE

Child Pugh
A 0 0% A
Child Pugh
B 2 25% B

C 6 75%

NUMBER OF HEPATIC DOSE ADJUSTMENTS DONE DURING THE STUDY PERIOD:

Among 8 hepatic impairment patients, 1(12%) patient required dose adjustment and remaining 7(88%) required no dose adjustment.
adjustment No adjustment

13%

NO. OF DRUGS PERCENTAGE

Adjustment 1 12%
No adjustment 7 88%

88%
TYPE OF DRUG DOSE ADJUSTMENTS:
Out of 24 drugs that had dose adjustments, 14 single drugs were adjusted and remaining 10 dual drugs were adjusted.

TYPES OF DRUG DOSE ADJUSTMENT NUMBER OF DRUGS PERCENTAGE%

Single drugs 14 58%

Combination drugs 10 42%

10; 42%

14; 58%

Single drugs Combination drugs

RENAL DOSE ADJUSTMENT BASED ON CATEGORY OF DRUGS:
Among 23 renal dose adjustments 20 drugs were antibiotics, 2 drugs were statins and 1 drug was anticoagulant.
antibiotics statins anticoagulants

4%
CATEGORY NUMBER OF DRUGS PERCENTAGE 9%

Antibiotics 20 87%
Statins 2 9%
Anticoagulants 1 4%

87%

RENAL DOSE ADJUSTMENT OF ANTIBIOTICS:

Out of 20 renally adjusted antibiotics 8 drugs were meropenem, 7 drugs were piperacillin tazobactam, 2 drugs were
5%
aztreonam 5%
5%

10% 40%

ANTIBIOTICS NUMBER OF DRUGS PERCENTAGE%

Meropenem 8 40%
Piperacillin + tazobactam 7 35%
Aztreonam 2 10%
Cefoperazone + sulbactam 1 5%
Ceftazidime + avibactam 1 5%
Imipenem + cilastatin 1 5%
35%

meropenam piperacillin tazobactum azreonam

cefoperazone sulbactum ceftazidime avibactum imipenam cilastatin
NUMBER OF RENAL IMPAIRMENT PATIENTS UNDERWENT EXTRACORPOREAL REMOVAL OF DRUGS DURING THE
STUDY PERIOD

Out of 101 renal impairment patients 4 patients were in hemodialysis, 2 patients were in continuous renal replacement therapy (CRRT), 2
patients were in sustained low efficiency dialysis (SLED), and remaining 93 patients were not on dialysis .

EXTRACORPOREAL DRUG REMOVAL TECHNIQUE NUMBER OF PATIENTS PERCENTAGE

Haemodialysis 4 4%
CRRT 2 2%
SLED 2 2%
Not on dialysis 93 92%

HD CRRT SLED NOT ON DIALYSIS

HOSPITALIZATION OF PATIENTS DURING THE STUDY PERIOD:

Among 109 patients, 59(54%) patients had short hospital stay (1-6 days), 45(41%) patients had long hospital stay (>7 days) and
5(5%) patients discharged against medical advice (AMA).

HOSPITALIZATION NUMBER OF PATIENTS PERCENTAGE

Short(1-6days) 59 54%
Long(>7days) 45 41%
AMA 5 5%

60
Number of patients

50

40

30

20

10

0
LONG SHORT AMA
Hospitalization
PROGRESS OF PATIENTS DURING THE STUDY PERIOD
Among 109 patients included in the study, 4 (3.66%)hepatic and 20(18.34%) renal impairment patients were declared, 2(1.83%)
hepatic and 45(41.28%) renal patients were recovered and 2(1.83%) hepatic and 35(32.11%) renal patients were recovering. In
this study recovery percentage is higher in renal patients when compared to hepatic patients.

PROGRESS HEPATIC PERCENTAGE RENAL PERCENTAGE

Declared 4 3.66% 20 18.34%
Recovered 2 1.83% 45 41.28%
Recovering 2 1.83% 35 32.11%

50
45
40
35
Number of patients

30
25
20
15
10
5
0
declared recovered recovering
Progress

hepatic renal
OVERDOSING AND UNDERDOSING IN DOSE ADJUSTMENT:
Among 24 dose adjustments, 17(71%) drugs were overdosed, 4(17%) drugs were underdosed, and 3(12%) drugs were
stopped.

PARAMETERS NUMBER OF PATIENTS PERCENTAGE

Over dosed 17 71%
Under dosed 4 17%
Stopped 3 12%

stopped
Parameters

under dosing

over dosing

0 2 4 6 8 10 12 14 16 18
number of patients
DISTRIBUTION OF PATIENTS BASED ON APACHE II SCORE AMONG STUDY POPULATION
Among 109 patients, 1 patient’s APACHE II score was between 10 and 14, 15(13.7%) patient’s scores were between 20 and 24,
30(27.6%) patient’s scores were between 25 and 29, another 30(27.6%) patient’s scores were between 30 and 34 and 33(30.2%)
patient’s scores were more than 34.

APACHE II SCORE NUMBER OF PATIENTS MORTALITY PERCENTAGE

0 to 9 0 4% 0%
10 to 14 1 15% 0.9%
15 to 19 0 25% 0%
20 to 24 15 40% 13.7%
25 to 29 30 55% 27.6%
30 to 34 30 75% 27.6%
35 >34 33 85% 30.2%
30
Number of patients

25

20

15

10

0
0 to 9 10 to 14 15 to 19 20 to 24 25 to 29 30 to 34 >34
APACHE score
TOTAL NUMBER OF PATIENTS ON VENTILATION DURING DISTRIBUTION OF PATIENTS ON VENTILATORY
THE STUDY PERIOD SUPPORT BASED ON TYPE OF VENTILATION
TECHNIQUE:
Among 109 patients included in the study, 59(54%) patients were on
mechanical ventilation and 50(46%) patients were not on mechanical Among 59 patients who were in ventilation, 36(61%) patients
ventilation had ETT and 23(39%) patients had NIV.

PARAMETERS NUMBER OF PERCENTAGE TYPE OF NUMBER OF PATIENTS PERCENTAGE

PATIENTS VENTILATION (n=59)
On ventilation 59 54% ETT 36 61%
Not on ventilation 50 46% NIV 23 39%

NIV
39%

Not on venti-
lation
46%

On ventilation
54% ETT
61%
TOTAL NUMBER OF PATIENTS ON INOTROPES AMONG DISTRIBUTION OF INOTROPES AMONG THE STUDY
STUDY POPULATION: POPULATION:
Among 109 patients included in the study, 26(24%) patients were on Among the study population 23(52.2%) noradrenaline, 7(15.9%)
inotropes and 83(76%) patients were not on any inotropes vasopressin, 7(15.9%) adrenaline, 5(11.3%) dobutamine and
2(4.54%) dopamine were given as inotropes.

PARAMETERS NUMBER OF PATIENTS PERCENTAGE TYPE OF INOTROPE NUMBER OF PERCENTAGE

INOTROPES
On inotropes 26 24%
Noradrenaline 23 52.2%
Not on inotropes 83 76% Vasopressin 7 15.9%
total 109 100% Adrenaline 7 15.9%
Dobutamine 5 11.3%
Dopamine 2 4.54%
Total 44 100%
24%
25

20

number of inotropes
15

10

76% 5

0
Noradrenaline Vasopressin Adrenaline Dobutamine Dopamine
on inotropes not on inotropes
type of inotropes
CONCLUSION
From our study we have the following conclusions,

 During the study period 23(21.1%) renal patients and 1(1%) hepatic patient had dose adjustment in intensive
care unit.
 We conclude that renal and hepatic dose adjustments played a crucial part in patient outcome in aspects of
health care, hospitalization and cost.
 While assessing the study population using APACHE score for mortality, 24(22%) patients were declared
due to their critical illness irrespective of the dose adjustments.
 Clinical pharmacist has vital role in patient care via dose adjustment.
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