Outcome Analysis of Anticoagulant Therapy in Critical Care Unit: The Need for a Pharmacy Managed Anticoagulant Service

Background: In our center, NCTCE, there are 2 intensive care units (general and cardiac), where critically ill patients are admitted and managed. Anticoagulation is usually indicated in such patients for atrial fibrillation, valve replacement and DVT prophylaxis. Objective: To determine the role of a clinical pharmacist in the therapeutic and clinical appraisal of such patients on anticoagulation. Materials and Method: Over a 2-year period (June 2015 –May 2017), a study design to determine the role of a clinical pharmacist in anticoagulant treatment was made in both ICU. This was a prospective longitudinal study. Here, demography, the anticoagulation on which interventions were made on, duration of admission, areas and determinants of a clinical pharmacist’s interventions were incorporated. Others included, were levels of intervention, acceptance and rejection of the interventions as well as the outcome. Results: During the study period, 168 patients were used. Male (72) and female (96), with a female to male ratio of 1:1.3. Indications for anticoagulation were DVT prophylaxis (14.88%), valves (83.90%) and AF (1.10%). Among the anticoagulants on which interventions were made on, warfarin was the highest (53.57%) while heparin was the least (2.90%). Duration of admission ranged from 2-40 days. Areas of intervention were on effectiveness of therapy (18.70%), drug-drug interactions (16.43%), adverse events (32.86%), dosage (11.05%), Kidney function (1.70%), adherence (6.70%) and drug selection (2.27%). Levels of intervention were at prescriber (30.51%), drug (38.56%), patient (25.42%) and laboratory (5.51%). The outcome was that majority of patients (78.74%) had their problems resolved. Conclusion: Anticoagulation therapy of patients in ICU requires precise damaging, monitoring and appropriate patient education so as to ensure that patients benefit maximally. A clinical pharmacist has a vital role to play in the above areas. Abbreviations: ICU: Intensive Care unit; PhRs: Pharmacist Recommendations; INR: International Normalized Ratio; ACCP: American Critical Care Physician; ADES: Adverse Events; VTE: Venous Thromboembolism; DTPS: Drug Therapies; DDI/DFI: Drug Drug/Dug Food Interactions; LMWH: Low Molecular Weight Heparins; CVP: Central Venous Pressure; CHADS: Congestive Heart failure, Hypertension, Age, Diabetes, Stoke DOI: 10.32474/ACR.2019.02.000126

Documented improvements in the management of infections, anticoagulant therapy, sedation, and analgesia for patients receiving mechanical ventilation and in emergency response help to justify the need for clinical pharmacy services for critically ill patients [1].

ICU patients have similar general risk factors for
venothrombosis and pulmonary embolism as well as arterial thromboembolism manifesting as stroke, mesenteric vascular occlusion and peripheral acute limb ischemia, with other patients (age, obesity, immobilization, past personal/family history of venothrombembolism, sepsis, cancer, stroke, respiratory, heart failure, pregnancy, trauma or recent surgery) [2][3][4]. In addition, they have other peculiar risk factors as a result of their illnesses and/ or treatment (vasopressor use, respiratory failure, heart failure, pharmacologic sedation, mechanical ventilation, central venous pressure (CVP) catheter and end stage renal failure) [3,5]. CVP catheter in the femoral, subclavian, internal jugular and superior vena cava veins have catheter related thrombosis occurrence rate ranging from 10-69%, 2-10%, 40-56% and 7-17% respectively [2,[5][6][7]. There is also 4-fold increased risk of pulmonary embolism from lower limb DVT in ICU patients [8]. Catheter related VTE risks increases proportionate to the duration of placement and if patient is not on LMWH anticoagulant [9]. Sepsis induce procoagulant status and favor catheter related VTE [6,10]. Vasopressor treatment is not an independent risk factor for VTE [5], however it is still linked with decreased absorption of subcutaneous heparin due to the vasoconstriction of peripheral blood vessels [11]. Platelet transfusion and high platelet levels, a common finding in ICU patients are risk factors for VTE [12]. Pharmacologic sedation is not an independent risk factor for VTE, however, when used alongside mechanical ventilation, it is. Mechanical ventilation by decreasing venous return and requiring sedation and immobilization is a risk for VTE, however, critical ill patients requiring long mechanical ventilation was compared with those who did not and the relationship between duration of mechanical ventilation and VTE was not established [2].
The implantation of an artificial heart valves exposes the patient to an increased risk of valve thrombosis and embolism; thus life-long oral anticoagulation is imperative [13]. The factors that lead to increased thromboembolism in such patients are the number of valves implanted, types of valves implanted (more in ball and cage variety), atrial fibrillation, left atrial enlargement, left ventricular dysfunction, clotting disorder and previous embolic events [14]. Atrial fibrillation is the most common arrhythmia in patients admitted in intensive care units (ICUs) and is associated with increased morbidity and mortality [15,16]. The problems of atrial fibrillation are low cardiac output, heart failure, hypotension and organ dysfunction as well as thromboembolism. CHADS algorithm defines the risk factors, which many critically ill patients have [17]. In addition, patients with rheumatic heart diseases, prosthetic heart valves, prio thromboembolism and persistent atrial thrombus detected by TEE as well as AF with complex atherosclerotic aortic plaque are considered at highest risk of embolic stroke if not on thromboprophylaxis [18]. In our ICU,   Figure 1 shows the age ranges of patients admitted during the study period. Highest range is 31-40 years. Least is 81-90 years.

Results
Also Figure 2 shows additional indications for anticoagulation, with mechanical prosthetic heart valves having the highest number while atrial fibrillation takes the least. Table 1 shows the anticoagulants administered and the number of interventions made on them. The highest number of interventions was made on warfarin, followed by enoxaparin while the least intervention was made on nonpharmacologic anticoagulant, elastic stockings.

Discussion
Intensive care Unit (ICU) is a potential area for drug therapy problems (DTPs): patients treated are complex patients [19]. Pharmacists have been incorporated into ICU multiprofessional staff to improve the care provided to patients, particularly by monitoring the drugs administered and assessing their efficacy, thus contributing to improving patient safety [24]. provision of patient education [30]. In this study, the determinants of the interventions ranged from effectiveness of therapy to drug selection, see Table 2. With this subgroup of effectiveness of therapy, international Normalized Ratio was used to monitor dosages which enabled the pharmacist to classify them as sub therapeutic, therapeutic and supratherapeutic.   In this same scenario, drug-drug or drug-food interactions were monitored and classified as minor, significant or serious, see Table 3. When the effectiveness of therapy was supra or sub therapeutic, and when the DDI/DFIs were significant or serious,

Conclusion
Anticoagulation treatment of patients in ICU requires precise dosing, a defined anticoagulant management programme, approved