Critical Care Pharmacotherapy PDF

Critical Care b. 2. 3. F.  lternatively, if estimated CrCl is less than 30 mL/minute/1.73 m2, dalteparin can be used because A it has minimal renal metabolism. c. Fondaparinux is contraindicated in patients with an estimated CrCl less than 30 mL/minute 1.73 m2. d. Low-dose unfractionated...

Critical Care b. 2. 3. F.  lternatively, if estimated CrCl is less than 30 mL/minute/1.73 m2, dalteparin can be used because A it has minimal renal metabolism. c. Fondaparinux is contraindicated in patients with an estimated CrCl less than 30 mL/minute 1.73 m2. d. Low-dose unfractionated heparin is minimally renally eliminated and is safe to use in patients with reduced kidney function. Overweight or underweight adults: For patients with obesity, some experts recommend increasing unfractionated heparin dose to 7500 units and LMWH prophylaxis doses by 30%–100% if body mass index (BMI) is greater than 40 kg/m2; a peak (4 hours postdose) anti-Xa of 0.2–0.4 IU/mL is recommended. Note that these recommendations have not been validated in controlled trials and are considered expert opinion only (see Ann Pharmacother 2009;43:1064-83). Patients admitted with major traumatic injuries: Enoxaparin 30 mg every 12 hours is more effective than other regimens. Early initiation of pharmacologic prophylaxis (within 48 hr) in stable trauma patients was associated with lower incidence of VTE and no increased risk for bleeding complications or mortality (J Trauma Acute Care Surg 2021;90:54-63). Antithrombotic therapy and regional anesthesia 1. Critically ill patients often have their spinal meninges accessed for either therapeutic (epidural anesthesia, lumbar drains) or diagnostic (lumbar puncture) purposes. 2. The combination of antithrombotic medications with these techniques is associated with an elevated risk of spinal or epidural hematoma, which can lead to ischemia and paralysis. The risk is impacted by the dose, timing, and quantity of antithrombotic medications in relation to needle placement or catheter removal. 3. The American Society of Regional Anesthesia and Pain Medicine published guidelines on regional anesthesia in patients receiving antithrombotic or thrombolytic therapy. Pertinent details regarding VTE prophylaxis are listed below. For a comprehensive description of recommendations, refer to the guidelines (Reg Anesth Pain Med 2018;43:263-309). a. Subcutaneous unfractionated heparin (e.g., 5000 units every 8–12 hr) should be held 4–6 hours before needle placement or catheter removal, and the subsequent dose may be administered after at least 1 hour. Higher doses (e.g., at least 20,000 units/day) should be held for a longer interval. b. LMWH (e.g., enoxaparin 40 mg daily and 30 mg every 12 hr) should be held at least 12 hours before needle placement or catheter removal. Epidural catheters can be maintained with once daily dosing without other medications that impact hemostasis. In twice daily dosing, however, catheters may not be maintained. The subsequent dose may be administered at least 4 hours after catheter removal. Extra caution and consideration must be taken in patients with renal disease. i. The first dose of LMWH should be at least 2 hours after catheter removal. ii. Catheter removal should be at least 10–12 hours after the last LMWH dose (longer in patients with renal disease). c. Because of a lack of data, the use of fondaparinux should be avoided. d. Because of various DOAC regimens with differences in half-life and elimination, check for specific recommendations regarding regional analgesia. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-335 Critical Care G. Prevention of VTE: Pharmacologic options in critically ill patients Table 18. Prevention of Venous Thromboembolism: Pharmacologic Options Medication Unfractionated heparin Low-molecularweight heparin Fondaparinux Mechanism Factor Xa and indirect thrombin inhibition Factor Xa inhibition and some indirect thrombin inhibition Factor Xa inhibition Dosinga 5000 units SC two or three times daily Enoxaparin 40 mg SC daily Dalteparin 5000 units SC daily 2.5 mg SC daily Adjustment for Renal Dysfunction None CrCl < 30 mL/min/1.73 m2: enoxaparin 30 mg SC daily Contraindicated for CrCl < 30 mL/min/1.73 m2 a Patients within normal body mass index (BMI) range. SC = subcutaneously. X. PREVENTING VENTILATOR-ASSOCIATED PNEUMONIA A. T  he Institute for Healthcare Improvement has developed a ventilator bundle with the following elements that directly target ventilator-associated pneumonia and complications arising from it. 1. Head of the bed elevation: Maintain the head of the bed elevated (about 30–45 degrees). 2. Daily sedation interruptions and assessment of readiness to extubate 3. Stress ulcer prophylaxis 4. VTE prophylaxis 5. Daily oral care with chlorhexidine (0.12% oral rinse) B. Additional methods 1. Selective decontamination of the digestive tract a. It is a short course of antimicrobial therapy aimed at eradicating potential pathogens to minimize ICU-acquired infections. b. Selective decontamination is still not routinely performed and is not supported by the guidelines because of the risk of promoting antimicrobial resistance. 2. Endotracheal tubes coated in an antimicrobial (silver) reduce infection but are cost prohibitive in many centers. XI. NUTRITION SUPPORT IN CRITICALLY ILL PATIENTS A. General overview 1. Many critically ill patients have increased caloric and protein needs, and caloric deficit in these patients leads to excess morbidity (length of stay, infection) and mortality. 2. Skeletal muscle wasting and weakness occurring during critical illness may lead to prolonged mechanical ventilation and rehabilitation. 3. Ideally, nutrition should be provided within 24–48 hours of admission to the ICU. 4. Route of delivery (EN vs. PN) a. In general, EN is preferred to PN in patients with a functional GI tract and who are not malnourished. b. American and Canadian guidelines allow hypocaloric feeding during the first 7 days in previously well-nourished patients before consideration of PN. Supplemental PN Before 7 days is not recommended in patients without malnutrition. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-336 Critical Care c. d. The SSC guidelines suggest early (within 72 hr) initiation of EN in adult patients with sepsis or septic shock. The potential physiologic advantages include maintenance of gut integrity and reduction of the inflammatory response. PN is recommended for patients with extensive small bowel resection, chronic malabsorption, high-output enterocutaneous fistulas, severe malnutrition at baseline, suspected or confirmed GI ischemia, mechanical bowel obstruction, or persistent, severe hemodynamic instability. B. Estimating nutrition needs 1. Traditional biomarkers of nutrition (albumin, prealbumin, nitrogen balance) are not well validated in critically ill patients. 2. Indirect calorimetry and predictive equations can be used to determine energy needs in critically ill patients. a. Indirect calorimetry measures the metabolic rate, but it requires special equipment and trained staff and is subject to inaccuracies in some patient populations. Indirect calorimetry also provides a respiratory quotient (RQ), indicating substrate metabolism and allowing modification of macronutrient delivery (e.g., carbohydrates, fats, protein). i. RQ 1.0–1.3: Lipogenesis (overfeeding), hyperventilation, or system “leak” ii. RQ 0.9–1.0: Primary carbohydrate oxidation, metabolic acidosis iii. RQ 0.82–0.85: Normal, “mixed” substrate oxidation iv. RQ 0.80: Primary protein oxidation v. RQ 0.70: Primary fat oxidation, systemic inflammatory response syndrome, metabolic alkalosis, or ethanol oxidation vi. RQ less than 0.67 or greater than 1.3: Outside range; question test validity b. Several predictive equations for determining caloric goals have been used (e.g., Harris-Benedict, Penn State and modified Penn State, Ireton-Jones, Mifflin, and Swinamer equations). Each comes with variable accuracy rates compared with indirect calorimetry. A single equation has not been shown to be best across various ICU populations. c. Some guidelines recommend a 25-kcal/kg actual body weight target, but this approach may be too simplistic for most critically ill patients. d. The most recent ASPEN guidelines suggest feeding 12–25 kcal/kg in the first 7–10 days of the ICU stay, given no significant difference in clinical outcomes. Clinicians should use clinical judgment to adjust intake when EN or PN is associated with issues such as intolerance, glycemic variability, or respiratory acidosis. e. See the references for a review of the usefulness of predictive equations in critically ill patients. 3. Hypocaloric feeding a. The SSC recommends avoiding mandatory full caloric feeding in the first week, but suggests lowdose feeding (i.e., up to 500 kcal per day), advancing only as tolerated. b. One study showed that intentional underfeeding (60%–70% of target) of critically ill patients while providing 90%–100% of protein needs showed a significant reduction in hospital mortality. c. It is recommended that patients with obesity (BMI greater than 30 kg/m 2) can be fed at 60%–70% of target energy requirements or 11–14 kcal/kg actual body weight per day. Protein should be delivered in the range of 2–2.5 g/kg ideal body weight per day. 4. Protein needs a. The stress response in critical illness increases gluconeogenesis, which cannot be fully suppressed by exogenous glucose. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-337 Critical Care b. Protein intake of 1.2–2 g/kg of actual body weight is recommended in most critically ill patients. i. Patients on continuous renal replacement therapy may need up to 2.5 g/kg per day. ii. Protein restriction is generally not recommended for patients with acute kidney injury who are not receiving renal replacement. iii. Patients with extensive burn injury may need up to 3 g/kg per day. C. Enteral nutrition 1. It is important to recognize that the prescribed dose of EN is often not delivered to patients because of interruptions, intolerance, or many other reasons. Use of an EN protocol with guidance on initiation, advancement, and interruptions is essential. 2. “Trophic” feeding, or low-dose enteral feeding with the intent of maintaining GI tract function, is commonly used despite limited evidence. 3. EN can be delivered safely to patients receiving low-dose vasopressors. 4. Gastric versus small bowel (postpyloric) feeding delivery a. Delivery of EN directly into the small bowel may be associated with a reduction in pneumonia. b. In units where small bowel access is readily available, routine use of small bowel feeding is recommended. c. If small bowel access is not readily available, then small bowel feedings should be considered only for patients at high risk of intolerance to EN (on inotropes, continuous infusion of sedatives, or paralytic agents, or patients with high nasogastric drainage) or at high risk for regurgitation and aspiration (nursed in supine position) or who have repeatedly demonstrated intolerance of gastric feeds. 5. Gastric residual volumes a. There are no data indicating that interruption of gastric feeding for a specific residual volume prevents morbidity (aspiration pneumonia) in critically ill patients. The guidelines do not recommend routine checking of residual volume to assess aspiration risk. However, residuals may still be checked if there is concern for tolerance or to assess gastric motility, especially in patients with recent bowel surgery. b. A residual volume of 250–500 mL is recommended as a point where intervention should occur. Prokinetic agents such as metoclopramide and erythromycin may be given to decrease residuals and enhance gastrointestinal motility. D. Parenteral nutrition 1. Parenteral nutrition should be administered via the central vein whenever possible. Peripheral administration is possible, but it must be diluted and can lead to fluid overload with the increased volume of the solution. 2. Intravenous catheters intended for PN should not be used for any other purpose. 3. Blood glucose measurements should be taken at least every 4–6 hours for patients receiving PN during initiation and changes in carbohydrate content. E. S  upplemental antioxidants and immunomodulation: Supplemental antioxidants and immunomodulating micronutrients (vitamin E, selenium, fish oils, arginine, glutamine, zinc) are not recommended for general critically ill patients. F. In addition to the SSC, the American Society of Parenteral and Enteral Nutrition publishes guidelines in conjunction with the Society of Critical Care Medicine (Crit Care Med 2016;44:390-438). G. Further guidance: See “Fluids, Electrolytes, and Nutrition” chapter. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-338 Critical Care Patient Case Questions 14 and 15 pertain to the following case. A 75-year-old woman (height 65 inches [165 cm], weight 68 kg) who is intubated needs mechanical ventilation for an acute exacerbation of chronic obstructive pulmonary disease. She has a medical history of heart failure and hypertension. Her laboratory values are normal except for a creatinine level of 1.9 mg/dL. 14. Which is the most appropriate recommendation to prevent VTE in this patient? A. Initiate intermittent pneumatic compression. B. Administer fondaparinux 2.5 mg subcutaneously once daily. C. Administer enoxaparin 30 mg subcutaneously twice daily. D. Administer heparin 5000 units subcutaneously three times daily. 15. T  hree days later, the patient continues to need mechanical ventilation. Enteral nutrition has been initiated through her nasogastric feeding tube and has gradually been increased to her goal of 45 mL/hour. Over the past day, her gastric residuals are consistently 300–350 mL. Which statement is most appropriate to optimize this patient’s nutrition support? A. Change to PN. B. Add metoclopramide 5 mg intravenously every 6 hours. C. Change feeds to a more concentrated formula. D. Decrease tube feeds to 10 mL/hour. XII. INTRACRANIAL HEMORRHAGE A. General overview 1. Intracranial hemorrhage (ICH) is a broad term that encompasses many clinical scenarios. Goals of care are to minimize hemorrhage expansion and to treat associated organ dysfunction, thereby decreasing mortality and improving quality of life. 2. ICH is classified by the anatomic location of the bleeding. a. Intraparenchymal hemorrhage (IPH): Nontraumatic bleeding into the brain parenchyma b. Subarachnoid hemorrhage (SAH): Bleeding into the space between the pia and arachnoid membranes that can be caused by rupture of a cerebral aneurysm, bleeding from arteriovenous malformations, tumors, amyloid angiopathy, or vasculopathy. Patients may present early on with the classic “worst headache of my life.” c. Subdural hematoma (SDH) – Bleeding between the dura and arachnoid space d. Epidural hematoma (EDH) – Bleeding between the dura and the bone 3. Subdural and epidural hematomas are usually caused by traumatic injury. 4. Severity of ICH and resulting neurologic injury guide diagnostic tests, treatment, and prognosis. Commonly used scales include the Glasgow Coma Scale (GCS; Table 19) to assess the level of consciousness and the National Institutes of Health Stroke Scale. Disease-specific scales are also used for SAH and IPH. The Hunt and Hess scale is a qualitative scale that rates patients with SAH from 1 (no symptoms) to 5 (deeply comatose). The Fisher scale rates the amount of blood present in patients with SAH from 1 (no blood visualized) to 4 (diffuse SAH, ICH, or intraventricular hemorrhage present). Because the etiologies of IPH and SAH are different, the ICH score is used for IPH. The ICH score is a composite score consisting of hemorrhage size, age, site of hemorrhage, and GCS scores and ranges from 0 (best) to 6 (worst). ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-339 AL GRAWANY Critical Care Table 19. Glasgow Coma Scale Axes Eye Opening Does not open eyes Opens eyes in response to painful stimuli Opens eyes in response to voice Opens eyes spontaneously Motor Response Makes no movements Extension to painful stimuli Abnormal flexion to painful stimuli Flexion or withdrawal to painful stimuli Localizes painful stimuli Obeys commands Verbal Response Makes no sounds Incomprehensible sounds Utters appropriate words Confused, disoriented Oriented, converses normally Score 1 2 3 4 1 2 3 4 5 6 1 2 3 4 5 B. Risk factors 1. Hypertension is the most common risk factor. 2. Use of fibrinolytic (e.g., alteplase), anticoagulant, and antiplatelet medications 3. Amyloid angiopathy 4. Intracranial aneurysm a. Rupture may be spontaneous or may result from exertion or hypertension. b. Risk factors for rupture include tobacco use, hypertension, cocaine use, a history of SAH, familial history of SAH, large aneurysm size, female sex, connective tissue disease, and older age. 5. Liver failure–induced coagulopathy 6. Mycotic aneurysms C. Management 1. Blood pressure control a. Acute hypertension should be controlled after the diagnosis of SAH. The goal blood pressure has not been definitively established. AHA Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage recommend balancing the risk of stroke, rebleeding because of hypertension, and maintenance of cerebral perfusion pressure in determining a patient’s goal blood pressure. They further state that a goal systolic blood pressure less than 160 mm Hg is reasonable. b. Elevated blood pressure is associated with greater hematoma expansion, neurologic deterioration, death, and dependency after ICH. The 2022 AHA/ASA guidelines for managing spontaneous intracerebral hemorrhage recommend acute lowering of SBP to 140 mm Hg for patients with SBP of 150–220 mm Hg and no contraindication to acute blood pressure treatment. Clinicians should use careful titration to ensure smooth and sustained control of blood pressure and avoid large variability to improve functional outcomes. The safety and efficacy data of blood pressure lowering are insufficient for patients with SBP greater than 220 mm Hg, but it may be reasonable to consider aggressive blood pressure reduction with a continuous intravenous agent. INTERACT2 is the largest randomized trial assessing intensive treatment (SBP less than 140 mm Hg) versus ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-340 Critical Care 2. 3. 4. 5. 6. guideline-recommended treatment (SBP less than 180 mm Hg). There was no difference in death or disability at 90 days, but functional outcomes were improved with intensive blood pressure control. c. Blood pressure should be controlled with an intravenous, titratable agent such as nicardipine or clevidipine. Comparisons of agents and clinical outcomes are lacking. Details on antihypertensive agents are available in the “Acute Care in Cardiology” chapter. Antifibrinolytic therapy a. For patients who will have a delay in surgical intervention after an aneurysmal SAH, short-term (less than 72 hours or until angiography) treatment with tranexamic acid or aminocaproic acid (preferred) is reasonable. b. The TICH-2 trial evaluating tranexamic acid in acute ICH found no difference in functional status or mortality at 90 days. Because of a lack of benefit, tranexamic acid should not routinely be given in this patient population. c. Many different dosing protocols exist for aminocaproic acid and tranexamic acid. Typically, aminocaproic acid is administered as a 4- to 5-g load followed by 1 g/hour. Tranexamic acid is administered as a 1-g load followed by 1 g infused over 8 hours. d. Patients who receive antifibrinolytic therapy should be monitored for the development of a VTE. Coagulation factors: In a study of ICH not caused by anticoagulant therapy, recombinant activated factor VII decreased the size of ICH but did not improve functional outcomes. Meta-analyses showed no benefit on hematoma expansion, functional outcomes, or adverse events. See “Anticoagulation” chapter for information on anticoagulant-related ICH. Seizure prophylaxis a. The incidence of seizures after SAH may reach 20%, seen mainly at the time of rupture, with the incidence decreasing after treatment. The use of antiepileptic drugs is controversial and may stem from earlier studies that used primarily phenytoin for prophylaxis. Current guidelines state that prophylaxis can be considered in the immediate posthemorrhage period. b. Phenytoin is subject to drug interactions, notably with nimodipine (decreasing nimodipine serum concentrations). Both the AHA and the Neurocritical Care Society guidelines recommend against the use of phenytoin because of adverse outcomes. c. Levetiracetam is generally considered a safer antiepileptic drug, but data supporting its use are limited. d. Compared with SAH, the incidence of seizures in ICH is estimated to be the same or slightly higher; however, seizures can present at the onset or occur late in therapy because of scarring. The 2022 AHA guidelines on ICH recommend against prophylactic anticonvulsants because evidence has not consistently identified benefit or harm with respect to functional outcomes. Vasospasm a. Vasospasm is the acute narrowing of the cerebral arteries after aneurysmal SAH. It is most common during the first 7–10 days after aneurysm rupture and the risk typically resolves after 21 days. Untreated, vasospasm leads to delayed cerebral ischemia, a major cause of death and disability. b. Oral nimodipine 60 mg every 4 hours for 21 days should be administered in all patients with aneurysmal SAH. Although this agent does not decrease the incidence of vasospasm it has been shown to improve outcomes. For patients who are unable to tolerate 60 mg every 4 hours because of hypotension, 30 mg every 2 hours is also an option. c. Triple-H therapy (hypertension, hypervolemia, hemodilution) is no longer recommended. Euvolemia should be maintained in all patients. Large volumes of hypotonic fluids should be avoided. Microsurgical clip obliteration by craniotomy and endovascular coiling are both interventions for aneurysmal SAH that should be performed as early as possible. Determination regarding which procedure yields better outcomes is ongoing. Advancements in both approaches have improved the rate of survival and lowered the rate of disability. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-341