Periodic review of drug administration practices, as well as an analysis of any error committed, is necessary to develop optimal patient care. The need of an optimal patient care cannot be overemphasized in intensive care units (ICUs). Since the condition of the patient in ICUs is usually very unstable, any small error in the therapy could lead to deterioration in his condition. Doses adjustments and drug interactions prevention are two major parts of pharmacy care, which is lacking in most of the multispeciality hospitals in developing countries. Therefore, every institution should have a quality assurance plan in place, which details the process for responding when an error has been made. For example: How to do the root cause analysis, what all areas to be screened, and methods for counselling the healthcare providers involved. The role of pharmacologist or pharmacist in ICUs is still not clear but with the rising rates of newer drugs launched in the market and adverse drug reactions plus drug interaction related to these newer products, it is quite essential to think on such serious matters related to patient care.
Critically ill adults and children who require comprehensive, specialised care by the members of the ICU Care Team and continuous care including monitoring, assessment, evaluation and treatment of their life-threatening conditions and who are at risk of serious complications should be treated in intensive care unit. Care in the ICU is provided by a multidisciplinary ICU Care Team, which is composed of specially trained physicians, nurses, and other professionals. Each professional brings his or her particular expertise to the team, collaborating on a plan of care and treatment for each patient, based upon his or her individual needs and conditions.
The increasing use of high-tech drugs and sophisticated drug delivery methods would seem to make the ICU a prime area for specialist pharmacy practitioners. Montazeri and Cook showed the benefits of the pharmacist in a multidisciplinary ICU set-up in Canada, and cost savings from having pharmacist input to a medical ICU in the US have also been demonstrated. Leape and colleagues showed a lower rate of adverse drug events associated with pharmacist involvement on prescribing rounds in a medical ICU in the US. The benefits of specialist renal pharmacists have been documented. In a multicentric study in Australia out of 29,269 critically ill patients admitted during the study period, 1738 (5.7 per cent) had acute renal failure during their ICU stay, including 1260 who were treated with RRT. Changes in liver perfusion may have a substantial influence on the pharmacokinetics of drugs with flow-controlled metabolism.
Role of kidney and liver
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. Drug bioavailability is also controlled by the liver's capacity to clear the drug from the circulation. This depends on both hepatic blood flow and the efficiency of drug removal by hepatocytes (extraction ratio). If the latter is very high, drug clearance primarily depends on hepatic blood flow (eg, propranolol, lidocaine), whereas flow has relatively little effect on drugs that are slowly cleared by the liver (eg, theophylline, warfarin, diazepam). Most drugs are cleared at intermediate rates, which are affected by alterations in both hepatic flow and extraction capacity.
Both the organs kidney and the liver are vital to maintain the normal drug pharmacokinetics. In ICU, the patients with 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.
Renal function test
Kidney function test is a collective term for a variety of individual tests and procedures that can be done to evaluate how well kidneys are functioning.
Description
Many conditions can affect the ability of the kidneys to carry out their vital function. A number of clinical laboratory tests that help to determine the cause and extent of kidney dysfunction. These tests are done on urine as well as blood samples.
Urine test
" Creatinine Clearance Test: This test evaluates how efficiently the kidneys clear a substance called creatine from the blood. Creatinine, a waste product of muscle energy metabolism.
" Urea Clearance Test: Urea is a waste product of protein metabolism and excreted in the urine. This test requires a blood sample to measure the amount of urea in the blood and two urine specimens.
Blood test
" Blood Urea Nitrogen Test (BUN): Kidneys regulate BUN levels, filter urea in the glomeruli and reabsorb it in the tubules. BUN increases during dehydration. Excretion is markedly decreased when GFR drops. (Longer the tubular fluid remains in the kidney, the greater the reabsorption of urea into the blood).
" Serum Creatinine: A byproduct of creatinine metabolism in muscle. It is filtered in the glomeruli, but not reabsorbed in the tubules. Therefore, blood values depend closely on GFR. Normal creatinine level is proportional to muscle mass, example, small woman - 0.5 mg/100 ml blood, man - 1.0 mg/100 ml, muscular man - 11.4 mg/100 ml.
*If value doubles, GFR - and renal function - probably have fallen to half of normal state.
*If value triples - suggests 75 per cent loss of renal function.
*Values of 10 mg/100 ml - 90 per cent loss of function
Normal results
Urine test:
" Creatinine Clearance: For 24-hour urine. Normal results: 90 - 139 ml/min for adults; 80 - 125 ml/ min for females.
" Urea Clearance: Normal results: 64 - 99 ml/min.
Blood test:
" Blood Urea Nitrogen (BUN): 8-20 mg/dl.
" Serum Creatinine (sr. cr): 0.8-1.2 mg/dl.
If these results exceeds to their normal value there is necessary to adjust the dose of drug in renal dysfunction.
Creatinine clearance calculation:
Simplified 4-variable MDRD study formula
GFR = 186.3 x (SCR)-1.154 x (age in years)-0.203 x 1.212 (if patient is black) x 0.742 (if female). May represent the most accurate choice for patients with chronic kidney disease.
Assessment of liver function: Child-Pugh System
Hepatic parameters Points scored for observed findings
1 2 3
Encephalopathy grade* None 1 or 2 3 or 4
Ascites Absent Slight Moderate
Serum bilirubin, mg/dL <2 2 to 3 >3
Serum albumin, g/dL >3.5 2.8 to 3.5 <2.8
Prothrombin time, sec prolonged <4 4 to 6 >6
Note: Encephalopathy grade*:
Grade0: Normal consciousness, personality, neurological examination, EEG
Grade 1: Restless, sleep disturbed, irritable/agitated, tremor, impaired handwriting, 5 cps waves
Grade 2: Lethargic, time-disoriented, inappropriate, asterixis, ataxia, slow triphasic waves
Grade 3: Somnolent, stuporous, place-disoriented, hyperactive reflexes, rigidity, slower waves
Grade 4: Unrousable coma, no personality/behavior, decerebrate, slow 2-3 cps delta activity
Assessment
1. Class A or mild: If 5 or 6 points; Good operative risk
2. Class B or moderate: If 7 to 9 points; Moderate risk
3. Class C or severe: If 10 to 15 points; Poor operative risk
(Developed for surgical evaluation of alcoholic cirrhotic)
Maddrey discriminant function (df)
df = 4.6 x (prothrombin time, in seconds) + serum total bilirubin, mg/dL
Interpretation of the df values in patients with acute alcoholic hepatitis was that the disease was not severe if df <54, was severe if 55 to 92, and probably lethal if 93 or more and untreated.
The df was modified in a later study by Carithers, et al., (1989) to use the prolongation of prothrombin time above normal control values and to divide the serum bilirubin by 17.1 to give mmol/L. Patients with modified df values of 32 or more were entered into a study of methylprednisolone treatment, corresponding to Maddrey df values of approximately 106.
Hepatic contribution to the elimination of the compound
For no hepatic contribution to the elimination of the compound: If greater than 90 per cent of the dose is excreted in the urine as unchanged drug, hepatic impairment would not be expected to have a significant effect on elimination.
For limited (<20%) hepatic elimination: Wide Therapeutic Range - Because greater than 80% of the dose is excreted in the urine as unchanged drug, hepatic impairment would not be expected to lead to unsafe systemic exposure. Narrow Therapeutic Range - Because the usual doses of the drug are close to doses that can cause adverse effects, and there is in-vitro or in-vivo evidence of hepatic contribution to the elimination, hepatic impairment could lead to an increased exposure and possibly an increase in adverse effects. Patients with impaired liver function may require reduced doses of or longer dosing intervals. If drug is used, close monitoring of patients with impaired liver function is important.
For extensive (>20%) hepatic elimination: Wide Therapeutic Range - Because there is in-vitro or in-vivo evidence of extensive hepatic contribution to the elimination, hepatic impairment would be expected to have significant effects on the pharmacokinetics. Caution should be exercised during the use. Patients with impaired liver function may require reduced doses or longer dosing intervals. Narrow Therapeutic Range - Because there is in-vitro or in-vivo evidence of extensive hepatic contribution to the elimination, hepatic impairment would be expected to have significant effects on pharmacokinetics. Drug should be avoided or used with great caution in this patient population.
For unknown hepatic elimination: Consider the compound as extensively metabolised and use the above format.
(The authors are with
Indraprastha Apollo Hospital, New Delhi)