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The aim of this study is to evaluate the drug utilization pattern and pharmacoeconomic analysis in critical care unit (CCU).
Indoor case papers of patients admitted in CCU between January 2008 and December 2010 were analyzed for demographic variables; indications; duration of CCU stay; proportion of common drugs used. Use of antimicrobials was evaluated based on the culture report and empirical regimen used. Defined daily dose (DDD)/100 bed-days were calculated. Various World Health Organization prescribing indicators were evaluated. Cost of drugs was calculated from Indian Drug Review (2010).
A total of 397 cases were evaluated with a mean age of 44.62 years (95% confidence interval [CI]: 42.56-46.69). Average duration of CCU stay was 4.15 days (95% CI: 3.79-4.51). The average number of drugs prescribed per patient was 13.54 (95% CI: 13.05-14.04). Total drug utilization in terms of DDD/100 bed-days was 226.27. Metronidazole, cefotaxime, atropine, adrenaline, dopamine, dobutamine, deriphyllin, ranitidine, metoclopramide and furosemide were prescribed in more than 30% cases. Number of antimicrobials prescribed per patient was 2.50 (95% CI: 2.37-2.66). Cefotaxime + metronidazole (26.70%) were the most common empirical regimen used. Average cost of treatment per patient was Rs 3225.70 (95% CI: 2749.8-3701.6). Higher economic burden was noted among expired patients and admitted due to medical + surgical indication (P < 0.05).
Poly-pharmacy and use of antimicrobials without culture report is a common problem in CCU.
The marketing, distribution, prescription and use of drugs in a society, with special emphasis on resulting medical, social and economic consequences is known as drug utilization research. It is an important tool to study the clinical use of drugs in populations and its impact on health-care system.[1,2] The critical care unit (CCU) is a setting where the multiple medications are prescribed to patients. The costs of hospitalization and treatment are high in CCU as patients are seriously ill and often suffer from the chronic critical illnesses. CCU services use higher economic resources due to frequent use of high priced drugs and antimicrobial agents. Due to availability of limited funds in developing countries, drugs should be prescribed rationally so that the available funds can be utilized optimally. The CCU is considered as the epicenter of antimicrobial resistance and it is an important problem influencing patient outcomes. Incidence of poor treatment response and adverse reactions increase due to critical conditions of patients and use of multiple medications with altered pharmacokinetic and pharmacodynamic conditions. Periodic evaluation of drug utilization in the CCU is necessary for optimization of health care system, proper use of resources and making prescription policy.
The assumed average maintenance dose per day for a drug used for its main indication in adults is called defined daily dose (DDD).[6,7] Use of DDD is an important tool to compare the drug utilization among different clinical setups within a country and between different countries. DDD/100 bed-days provide a rough estimate of drug consumption in hospital inpatients and it is a fixed unit of measurement independent of formulation and price.[6,7] In the present study, we have evaluated the drug utilization pattern and calculated the DDD for the drugs used in CCU of a tertiary care hospital.
A retrospective study was carried out, after the permission from Institutional Review Board, Government Medical College, Bhavnagar, Gujarat, India. Indoor case papers of the patients admitted in CCU between January 2008 and December 2010 were collected from the medical record section of Sir Takhtsinhji General Hospital, Bhavnagar, Gujarat, India. Data were collected for age, gender, diagnosis, duration of CCU stay, laboratory investigations and treatment provided during the stay in CCU. Culture and sensitivity reports and adverse drug reaction if mentioned in case papers were also noted.
Data were analyzed for demographic variables; indication of admission in CCU and systems involved; duration of CCU stay; total number of drugs prescribed per patient; proportion of common group and particular drugs used; the total number of antimicrobials and inotropes used per patient; use of fixed dose combinations (FDCs); use of generic and brand drugs; use of oral and parenteral formulations; use of the five most costliest drugs; organisms isolated and their antimicrobial sensitivity and outcome of the patient. Total cost of drugs per patient was calculated from the Indian Drug Review (2010). Total cost of laboratory investigations per patient was calculated according to the price list of Bhavnagar Pathologist Association. The drugs were classified according to the Anatomical Therapeutic Chemical classification based on their chemical, pharmacological and therapeutic properties. The drug utilization was measured in DDD/100 bed-days.
DDD/100 bed-days were calculated using the following equation:
In our CCU, bed strength was 10 and average bed occupancy rate was 0.6 during the study period.
Data were expressed as proportions and mean (95% confidence interval [CI]). Mostly descriptive statistics were used. Comparisons of the total number of drugs prescribed per patient; duration of CCU stay; and cost of total treatment, antimicrobials and inotropes per patient were performed using the Kruskal-Wallis test followed by Dunn's multiple comparison test between patients admitted with medical, surgical and medical + surgical indications. Same parameters were compared between survived and expired patients using Mann-Whitney U-test. Statistical comparison was performed by using GraphPad Instat 3.0 (trial version). GraphPad Software Inc. 7825 Fay Avenue, Suite 230 La Jolla, CA 92037 USA. P < 0.05 was considered to be statistically significant.
A total of 397 indoor case papers of CCU were scrutinized. 2 (0.5%) patients were below 12 years; 221 (55.67%) patients were between 12 and 49 years and 174 (43.83%) patients were above 49 years of age group. The mean age of admitted patients was 44.62 years (95% CI: 42.56-46.69 years). A total 246 (61.96%) patients were male and 151 (38.04%) were female. Total 278 (70.03%), 71 (17.88%) and 48 (12.09%) patients were admitted with medical, surgical and medical + surgical indications respectively. The common indications for the admission were septicemia (35.37%), head injury (32.39%), complicated acute abdomen (25.35%), cardiovascular emergencies (21.94%) and organophosphate poisoning (17.27%). Total 170 (42.82%), 119 (29.97%) and 108 (27.21%) patients had one, two and more than two system involvement respectively. Cardio vascular (37.28%) was the most commonly involved system followed by gastro intestinal (36.52%), central nervous system (31.49%), respiratory (24.69%), renal (20.91%), hematology (17.63%), endocrine (8.82%) and genitourinary (2.77%).
The average duration of CCU stay was 4.15 days (95% CI: 3.79-4.51 days). A total of 5377 drugs (86.57% parenteral and 9.60% oral formulations) were prescribed in all patients. Total 319 different drugs (54.23% generic and 7.21% FDCs) were used. The minimum and maximum number of drugs prescribed to a single patient was 2 and 28, respectively. The average number of drugs prescribed per patient was 13.54 (95% CI: 13.05-14.04). Total drug utilization in CCU during the study period in terms of DDD/100 bed-days was 226.27. Metronidazole, cefotaxime, atropine, adrenaline, dopamine, dobutamine, etofylline + theophylline hydrate, ranitidine, metoclopramide and furosemide were prescribed in more than 30% of patients. Ceftriaxone, ciprofloxacin, noradrenaline, hydrocortisone, aspirin and pantoprazole were used in 10-30% of patients. Utilization pattern of various drugs and DDD/100 bed-days has been shown in Table 1. The commonly prescribed FDCs are described in Table 2. Among all the prescribed drugs, 18.48% were antimicrobials and 11.94% were inotropes. The antimicrobials and inotropes were used in 375 (94.45%) and 285 (71.79%) patients respectively. The average number of antimicrobials prescribed per patient was 2.50 (95% CI: 2.37-2.66). The average number of antimicrobials prescribed was significantly higher in expired than survived patients (2.80 [95% CI: 2.61-2.30] vs. 1.84 [95% CI: 1.7-2.06]; P < 0.05). The average number of inotropes prescribed per patient was 1.62 (95% CI: 1.49-1.75). 49 different antimicrobials were used. Cefotaxime + metronidazole (26.70%), ceftriaxone + metronidazole (16.88%), cefotaxime + gentamicin (7.81%) and ceftriaxone + gentamicin (3.78%) were the commonly used empirical regimens. The antibiotic sensitivity testing was performed in 46 (12.27%) patients. A total of 20 organisms were isolated in 17 (36.95%) patients. Change in antibiotic was performed in 10 cases (58.82%) based on isolated organisms and their sensitivity pattern. Isolated organisms were Klebsiella (40%), Pseudomonas (20%), Escherichia coli (10%), Staphylococcus aureus (10%), Candida (10%), Proteus vulgaris (5%) and Acinobactum (5%). Among 50% cases, S. aureus was sensitive to penicillin, oxacillin, cefazoline, ciprofloxacin, roxithromycin, tobramycin, amoxicillin + clavulanic acid, chloramphenicol and rifampicin. The sensitivity pattern of Gram-negative organisms to various antimicrobials is shown in Figure 1.
The average total cost of treatment per patient was Rs. 3225.70 (95% CI: Rs. 2749.8-Rs. 3701.6). The average total cost of antimicrobial drugs per patient was Rs. 1363.92 (95% CI: Rs. 1056.3-Rs. 1671.6). The average total cost of inotropes per patient was Rs. 262.31 (95% CI: Rs. 223.32-Rs. 301.30). Human-albumin, meropenem, methylprednisolone, piperacillin + tazobactum and enoxaparin sodium were the most costly drugs used in CCU. The average total cost of laboratory investigations per patient was Rs. 1521.41 (95% CI: Rs. 1379.3-Rs. 1663.5). The total cost of treatment in medical + surgical indications was significantly higher than patients with medical and surgical indication alone (P < 0.05). The comparison of the total number of drugs administered per patient, duration of CCU stay, cost per patient for total drugs, antimicrobials and inotropes in medical, surgical and medical + surgical indications are shown in Table 3. Total 274 (69%) patients were expired. The mortality rate for patients admitted with medical, surgical and medical + surgical indications were 71.58%, 52.11% and 79.17%, respectively. The most common cause of mortality was septicemia (21.91%). Total number of drugs administered per patient, duration of CCU stay and total cost per patient for survived and expired patients are shown in Table 4.
We evaluated 397 cases admitted in 10 bedded CCU of a tertiary care hospital.
Male preponderance (61.96%) is observed and male: female is in accordance with the previous reports. The average age is lesser than the previous reporting.[1,4,5,8] Patients were admitted for medical and surgical indications due to unavailability of separate intensive care units in our hospital. The most common indication for admission septicemia is in contrast to previous studies, which had reported cancer, cardiovascular emergencies and chronic obstructive pulmonary disease.[1,4,9] Head injury (32.39%), complicated cases of acute abdomen (25.35%) and cardiovascular emergencies (21.94%) were the other causes for admission in accordance with the previous studies.[1,9] Total 57.18% patients were having more than one illness, which is similar to other published report. The average duration of CCU stay (4.15 days) is similar to Shankar et al. (2005) and Yamashita et al. (2000) and lower than the Shankar et al. (2010), Curcio et al. (2011) and Tavallaee et al. (2010). Use of brand names (45.77%) and FDCs (7.21%) are comparatively lower in our study.[1,3] However, use of parenteral drugs (86.57%) is higher than previous studies.[1,4,9] The average total number of drugs prescribed per patient is higher than the reported in other studies.[1,3,4,9] Use of the total number of drugs and parenteral formulations may be related with the general condition of the admitted patients in different CCU settings. More critical patients were admitted in our CCU. Antimicrobial drugs (94.45%), antipeptic ulcer drugs (89.67%) and inotropes (71.79%) were the commonly utilized groups similar to John et al. However, cardiovascular drugs were the commonly used therapeutic class in other studies.[9,11,12]
Aggressive use of antipeptic ulcer drugs was to prevent stress induced ulcer. Atropine was used in patients of organophosphate poisoning, as a premedication and for bradycardia in late stages of septic shock. In critical care setting, it does not prevent all episodes of bradycardia and vasodilation when used before intubation.[13,14] Use of atropine is appropriate to counter bradycardia, cardiac hypo-oxygenation and hypoperfusion in septic shock. Adrenaline was mainly used for cardiac resuscitation. Dopamine, dobutamine and noradrenaline were used in combination with intravenous fluids for the patients of septic and cardiogenic shock. They were used to restore cardiac output, tissue perfusion and oxygenation. Inotropes are mainly effective in early stages of shock. Their late application for a prolonged period may harm the patient. The selection of individual inotropes is mainly empirical. There is no significant difference in mortality in patients of shock treated with dopamine and noradrenaline. However, use of dopamine is associated with cardiac arrhythmia.
Cephalosporins (73.30%), metronidazole (55.67%) and penicillins were the most commonly prescribed antimicrobials similar to previous studies.[3,4,9,10,11] However, aminoglycosides, meropenom, fluoroquinolones and piperacillin + tazobactum were the most utilized antimicrobials in other setup.[1,5,17] In our study, linezolid, meropenam, vancomycin, netilmycin and tobramycin were used as second line antimicrobials. The most common isolated organisms in our study is Klebsiella. Other studies had reported Pseudomonas,[17,18,19] E. coli[1,4,20] and S. aureus. Our study showed lower utilization of antibiotic sensitivity testing than Shalini et al. It is difficult to suggest the empirical antimicrobials for admitted patients due to underutilization of antibiotic sensitivity testing. The antimicrobial combination form the different classes should be considered for the septicemia due to high mortality. The selection of initial appropriate antibiotic regimen is important for reducing the mortality. The empirical combination antibiotic regimen directed against Gram-negative bacteria (carbapenem plus aminoglycoside or fluoroquinolone) reduces the initial inappropriate selection as compared to monotherapy alone. Amoniglycosides offer broader coverage than fluoroquinolones as combination agents for patients with this serious infection. The combination of carbapenems and aminoglycosides can be preferred in patients with severe sepsis and septic shock. There is an urgent need to enhance the utilization of antibiotic sensitivity testing for the better selection of antimicrobials and reduction of the mortality. Avoiding the use of unnecessary antibiotics helps to improve patient outcomes. In the present study, patients had spent approximately 40% of the total cost on antimicrobials. Preparation of antibiotic use policy helps in reduction in nosocomial infections and have a positive impact in the form of costs reductions.[25,26] The average cost of treatment prescribed per patient [Rs. 3225.7 ($ 57.74)] is higher in comparison with two studies by Shankar et al. in Nepal.[1,4] However, cost of treatment was lower than the Biswal et al. from India and Inan et al. from Turkey.[11,17] Biswal et al. had performed a study in the advanced referral center of India. Difference in the mean cost of treatment in our study than other studies may be due to variation in type and severity of the admitted patient, indications for the admission, different prescribing pattern or change in currency differences of various countries. Patient with medical + surgical indications has spent more money on the overall treatment. This is because of the use of higher expenditure medications. They have also spent more money for the antimicrobials. The cost for the treatment, antimicrobials and inotropes are higher in expired patients. This is due to the higher number of drugs used and duration of CCU stay.
The overall reported mortality in our study is higher than previously published reports.[4,9,12] This may be because of a higher number of patients with septicemia, head injury, poisoning and unavailability of the separate intensive care units for medical and surgical patients.
This study has certain limitations. Being a retrospective nature it was not possible to assess the rationality and quality of prescriptions. However, it helps to create drug utilization database in a tertiary care teaching hospital of developing country lacking separate medical and surgical intensive care units. These data provides no direct link with the outcomes associated with the use of the various categories of drugs. Line of treatment and selection of drugs varied by the physician-to-physician and it provide no data for the same.
In conclusion, antimicrobials and inotropes are frequently utilized drugs in CCU. Prescribing guideline is required to reduce the prevalent poly-pharmacy and to promote appropriate use of antimicrobial drugs based on the culture and sensitivity report.
We are sincerely thankful to record medical officer Dr. Vijay S. Boricha and staff of medical record section of Sir Takhtsinhji General Hospital, Bhavnagar for their kind help in providing indoor case papers for this study.
Source of Support: Nil
Conflict of Interest: None declared.