Appendix: Propofol is Associated with Favorable Outcomes Compared to. Benzodiazepines When Used for Sedation of Mechanically Ventilated ICU Patients

Transcription

1 ONLINE DATA SUPPLEMENT Appendix: Propofol is Associated with Favorable Outcomes Compared to Benzodiazepines When Used for Sedation of Mechanically Ventilated ICU Patients Table of Contents Page Methods Summary of Definitions and Explanations 2 Study Exclusions by Diagnosis 9 Appendix Table 1. Admission services 10 Appendix Figure 1. Enrollment flow diagram 11 Results Appendix Table 2. CIF 28-day ICU; propofol versus midazolam 12 Appendix Table 3. CIF 28-day ICU; propofol versus lorazepam 12 Appendix Table 4. CIF 28-days ventilator use; propofol versus midazolam 12 Appendix Table 5. CIF 28-days ventilator use; propofol versus lorazepam 12 Appendix Table 6. Post-treatment analyses propofol versus midazolam 13 Appendix Table 7. Post-treatment analyses propofol versus lorazepam 14

2 Summary of Definitions and Explanations Project IMPACT Database (Cerner Corporation, Kansas City, MO) Project IMPACT Registry Data: a request for multi-institutional data was submitted to the Project Impact research board on November 9 th, 2007, and approved on February 8 th, 2008 with data provided for analyses on June 24 th, A poster that presented a different set of data (different years) and a different method of analysis was presented at the 38 th Annual Critical Care Congress for Society of Critical Care Medicine January 31-February 4, Critical Care Managed Unit: the ICU is designated as a primary intensivist-staffed unit. The critical care physician director meets one or more of the following criteria: recognized by the institution as a critical care specialist within a specialty unit; has passed Critical Care Medicine Boards or is qualified to take the exam; trained in an ACGME critical care fellowship. APACHE II: calculated by Project IMPACT software on information collected from patient first 24 hours in the ICU. Surgical patient: a patient in whom a surgical procedure was performed within seven days prior to ICU admission. Includes; scheduled/elective defined as surgery performed within the 7 days prior to ICU admission and scheduled greater than 24 hours in advance; unscheduled/emergent postoperative defined as surgery was performed within the 7 days prior to ICU admission and scheduled less than 24 hours in advance. Surgical procedures are defined as invasive procedures that are performed either in the operating room or in a special procedure suite. The Project IMPACT database uses the American Medical Association Physicians Current Procedural Terminology (CPT ) to identify a surgical procedure. E2

3 Medical patient: a patient in whom no surgical procedure was performed or if a surgical procedure was performed, it was 8 days or more prior to ICU admission. Hemodynamic instability: the treatment with an infusion of a vasopressor or inotrope, defined as: norepinephrine, epinephrine, phenylephrine, isuprel, dopamine, vasopressin, dobutamine, or milrinone. Any of these agents required documented use as being given on any of the following days relative to intubation: one day before; the day of; or the day after intubation. Hospital length of stay: calculated as beginning with the date of ICU admission through to the date of hospital discharge. This calculation excludes days in the hospital prior to the ICU admission. Opiate Use: the treatment with a continuous infusion of an opiate, defined as: fentanyl, hydromorphone, morphine, alfentanil, or sufentanil. Any of these drugs required documented use as being given on any of the ventilator days: beginning with the day prior to ventilator start. Paralytic agent use: the treatment with a continuous infusion of a neuromuscular blocking agent; vecuronium, rocuronium, cisatracurium, atracurium, pancuronium. Hospital organization: Choices listed as; city/county, state, Veterans Administration, Military/Other Federal Government, community (for profit, non-academic), community (not for profit, non-academic), or academic (university based). Functional status on hospital admission: four possible choices Independent: the patient is living at home requiring no assistance in completing activities of daily living. This includes people who are homeless, or who are incarcerated, but otherwise physically and mentally functional. E3

4 Partially dependent: the patient is living at home, in a group home, or in a care facility and requires some assistance in completing the activities of daily living; the limitation(s) requiring assistance may be physical or mental. Fully dependent: the patient is living at home or in a care facility, and is unable to perform the activities of daily living; must be cared for by other(s); the limitations requiring assistance may be physical or mental. Unknown Chronic Health Conditions on ICU Admission: per APACHE II Gastrointestinal System: Biopsy proven cirrhosis and documented portal hypertension Episodes of past upper gastrointestinal bleeding attributed to portal hypertension Prior episodes of hepatic failure/encephalopathy/coma Cardiovascular System: The patient must have symptoms such as angina or shortness of breath at rest or on minimal exertion (New York Heart Association Class IV) and at least one of the following: severe coronary artery disease; severe valvular heart disease; severe cardiomyopathy Respiratory System: Chronic restrictive, obstructive or vascular disease resulting in severe mobility restriction Respirator dependency Documented chronic hypoxia, hypercapnia, secondary polycythemia or severe pulmonary hypertension (>40mmHg) E4

5 Renal System: Serum creatinine > 2.0 mg/dl Chronic renal compromise or insufficiency noted in their medical history with their most recent creatinine > 2.0 mg/dl Chronic hemo or peritoneal dialysis Nutrition Course: Enteral feeding: any commercially available feeding/nutritional support which is administered via the gut (nasogastric, duodenal, gastrostomy, duodenostomy, jejunostomy tubes); in a continuous, bolus, cyclic or intermittent manner Parenteral feeding: Total parenteral nutrition (TPN) administered via a central line Lipids TPN with lipids combination Peripheral parenteral nutrition (PPN): electrolyte solution similar to TPN with a lower dextrose concentration given peripherally PPN with lipids combined Organ Dysfunction Definitions During ICU Admission: Cardiovascular: Blood pressure criteria are present for at least 1 hour despite adequate fluid resuscitation (adequate fluid resuscitation requires the patient to have received typically at least 1-2 liters or 5-10 cc/kg of fluid): Arterial systolic BP < 90 mm Hg (unless known baseline is < 90) E5

6 OR Arterial systolic BP with 40 mm Hg drop from baseline OR Mean arterial pressure < 70 mm Hg OR Vasopressors are required to maintain BP > 90 mm Hg systolic or mean arterial pressure > 70 (if dopamine >5 mcg/kg/min) Serum lactate: elevated > normal limits per lab Respiratory: criteria apply to acute lung injury (ALI)*, not congestive heart failure or cardiogenic pulmonary edema; PaO 2 /FiO OR requires PEEP therapy > 5 cm H 2 O * ALI: is acute onset of respiratory failure with bilateral chest infiltrates on frontal chest x-ray not due to left-sided heart failure. [COPD patients may qualify for ALI. The definition of ALI excludes patients with chronic elevated cardiac filling pressures (i.e. left heart failure) or chronic infiltrative lung disease as the cause for chest x-ray or physiologic changes.] Renal: does not apply to patients on chronic dialysis Serum creatinine increased by more than 1 mg/dl from baseline after adequate fluid resuscitation (defined as requiring the patient to have received typically at least 1-2 liters or 5-10 ccc/kg of fluid). OR Serum creatinine 2 mg/dl in the absence of known baseline Hepatic: E6

7 Serum total bilirubin 2 mm/dl, acute not chronic Sepsis: a documented infection plus systemic inflammatory response. Systemic inflammatory response is considered to be present when at least two of the following is present: Temperature > 38 degrees centigrade or < 36 Heart rate > 90 beats per minute Hyperventilation, either respiratory rate > 20 per minute or PaCO 2 > 32 mm/hg White blood cell count > 12,000 mm 3, < 4,000 mm 3, or > 10% immature (band) forms Nosocomial Pneumonia: the diagnosis of nosocomial pneumonia was made while the patient was NOT receiving invasive mechanical ventilation. Pneumonia may be diagnosed two ways: 1. Rales and dullness to percussion on physical examination of the chest and any of the following: New onset of purulent sputum or change in character of sputum Organism isolated form blood culture OR Isolation of pathogen from specimen obtained by transtracheal aspirate, bronchial brushing or biopsy 2. Chest radiographic examination shows new or progressive infiltrate consolidation, cavitation or pleural effusion and any of the following: New onset of purulent sputum or change in character of sputum Organism isolated from blood culture E7

8 Isolation of pathogen from specimen obtained by transtracheal aspirate, bronchial brushing or biopsy Isolation of virus or detection of viral antigen in respiratory secretions Diagnostic single antibody titer (IgM) or fourfold increase in paired serum samples (IgG) for pathogen Histopathologic evidence of pneumonia (from CDC guidelines) Ventilator associated pneumonia: nosocomial pneumonia diagnosed while the patient was receiving invasive ventilation. Acute Respiratory Distress Syndrome: must have all findings present: Chest radiograph with new bilateral infiltrated seen on frontal chest radiograph PaO 2 /FiO No clinical evidence of left atrial hypertension based on chest radiograph OR pulmonary occlusion pressure < 18 mm Hg when measures Urinary tract infection: urine culture with > 100,000 organisms per ml Gastrointestinal bleed: upper or lower gastrointestinal blood loss requiring transfusion of blood products 1 unit Transfusion of red blood cells: inclusive of day before intubation through ventilation Steroid use: receiving scheduled (excludes per required need dosing) dosage of steroid medication during ventilation period; hydrocortisone, dexamethasone, or methylprednisolone. Haloperidol use: scheduled (excludes per required need) dosage Aminoglycoside use: received scheduled dosage of any of the following medications; gentamicin, tobramycin, or amikacin. E8

9 Study Exclusions by Admission Diagnoses: per International Classification of Disease (ICD-9): Diagnosis codes related to severe head injuries and/or cervical spine fractures with cord involvement were excluded from the study population. In the ICD-9 index, which is built into the Project IMPACT software, severe head injuries are specified as intracranial injuries with prolonged (more than 24 hours) loss of consciousness without the possibility of return to the pre-existing conscious level. Excluded codes included the following: 800.5, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , 850.4, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , E9

10 Admitting Service: There are a total of 43 admitting services from the Project IMPACT database. The table below shows the Project IMPACT admitting service and the distribution of admitting services used in the propensity analysis. Services were merged into major service groupings based on the individual low total volume of cases within and compared to other services. Table S1. Admitting Services Admitting Services within Project IMPACT N Admitting Services within Propensity Matching Anesthesia / Pain 4 Other Medicine Burn 1 Other Surgery Cardiac/Thoracic Surgery 422 Cardiac/Thoracic Surgery Cardiology 299 Cardiology Colorectal Surgery 77 Other Surgery Critical Care (Medical) 2,249 Critical Care (Medical) Critical Care (Surgical) 54 Other Surgery Dermatology 3 Other Medicine Endocrinology 7 Other Medicine ENT 136 ENT Family Practice 445 Family Practice Gastroenterology 74 Other Medicine General Medicine/Internal Medicine 3,175 General Medicine/Internal Medicine General Surgery 1,364 General Surgery Hematology 24 Other Medicine Hepatology 19 Other Medicine Infectious Disease 24 Other Medicine Nephrology 163 Nephrology Neurology 100 Other Medicine Neurosurgery 792 Neurosurgery OB-GYN 102 OB-GYN Oncology (Medical) 188 Oncology (Medical) Oncology (Surgical) 44 Other Surgery Ophthalmology (Medical) 0 Ophthalmology (Surgical) 1 Other Surgical Oral/Maxillary/Facial 11 Other Surgery Orthopedic Surgery 132 Orthopedic Surgery Pediatrics 2 Other Medicine Plastic Surgery 22 Other Surgery Psychiatry 1 Other Medicine Pulmonary 695 Pulmonary Rheumatology 3 Other Medicine Transplantation Cardiac 0 Transplantation Liver 111 Transplant Transplantation Other 6 Transplant Transplantation Renal 27 Transplant Transplantation Thoracic, Lung 10 Transplant Trauma 2,240 Trauma Urology/Genitourinary 87 Other Surgery Vascular 404 Vascular Physical Medicine & Rehabilitation 1 Other Medicine Vascular Interventional Radiology 5 Other Surgery Other 168 Other E10

11 Figure S1. Flow diagram of enrollment with exclusion criteria and group totals. E11

12 Table S2. Cumulative incidence function of death and discharge from ICU through ICU day-28 for propofol as compared to midazolam Sedative F i (t) Std Error 95% F i (t) Confidence Interval i =Death Midazolam Propofol i =Discharge from ICU Midazolam Propofol P-value (Gray's Test) <0.001 <0.001 F i (t) = cumulative incidence function Table S3. Cumulative incidence function of death and discharge from ICU through ICU day-28 for propofol as compared to lorazepam Sedative F i (t) * Std Error 95% F i (t) Confidence Interval i =Death Lorazepam Propofol i =Discharge from ICU Lorazepam Propofol P-value (Gray's Test) <0.001 F i (t) = cumulative incidence function Table S4. Cumulative incidence function of death and ventilator removal for propofol as compared to midazolam for patients through 28 days of consecutive ventilator use Sedative F i (t) Std Error 95% F i (t) Confidence Interval i =Death Midazolam Propofol i =Remove from vent Midazolam Propofol P-value (Gray's Test) <0.001 <0.001 F i (t) = cumulative incidence function Table S5. Cumulative incidence function of death and ventilator removal for propofol as compared to lorazepam for patients through 28 days of consecutive ventilator use Sedative F i (t) Std Error 95% F i (t) Confidence Interval P-value (Gray's Test) i =Death Lorazepam Propofol i =Remove from vent Lorazepam Propofol <0.001 F i (t) = cumulative incidence function E12

13 Table S6. Post-treatment variable results for propensity matched groups of propofol as compared to midazolam Post-treatment Variables * Midazolam (N=2,250) Propofol (N=2,250) P Value Odds Ratio/Mean Difference (95% Confidence Intervals) % of patients / mean ± SD Sedative Days on Ventilator 5.4± ±3.4 < ( ) Opiate Days on Ventilator 5.2± ±4.0 < ( ) Pulmonary Artery Catheter Use ( ) Cardio-pulmonary Resuscitation on Ventilator ( ) Organ Dysfunction After ICU Admission Cardiovascular ( ) Hepatic ( ) Renal ( ) Respiratory < ( ) Infections After ICU Admission Sepsis (Infection + Systemic Inflammatory Response) ( ) Abdominal Infection ( ) Blood Stream Infection ( ) Urinary Tract Infection ( ) Surgical Site Infection ( ) Vascular Access Infection ( ) ICU Complications Acute Respiratory Distress Syndrome ( ) Gastrointestinal Bleed ( ) Medications Continuous Infusion Neuromuscular Blocking Agent < ( ) Steroid Use While on Ventilator ( ) Haloperidol Use While on Ventilator ( ) Haloperidol Use in ICU ( ) Aminoglycoside Use in ICU ( ) Nutrition After ICU Admission Enteral Feeding ( ) Parental Nutrition < ( ) Transfusion Needs After ICU Admission Received Red Blood Cells in First 48 ICU ( ) Received Red Blood Cells in ICU < ( ) E13

14 Table S7. Post-treatment variable results for propensity matched groups of propofol as compared to lorazepam Post-treatment Variables * Lorazepam (N=1,054) Propofol (N=1,054) % of patients / Mean±SD P Value Odds Ratio/Mean Difference (95% Confidence Intervals) Sedative Days on Ventilator 5.1± ± ( ) Opiate Days on Ventilator 4.7± ±3.6 < ( ) Pulmonary Artery Catheter Use < ( ) Cardio-pulmonary Resuscitation on Ventilator ( ) Organ Dysfunction After ICU Admission Cardiovascular < ( ) Hepatic ( ) Renal ( ) Respiratory < ( ) Infections After ICU Admission Sepsis (Infection +Systemic Inflammatory Response) ( ) Abdominal Infection ( ) Blood Stream Infection < ( ) Urinary Tract Infection ( ) Surgical Site Infection ( ) Vascular Access Infection < ( ) ICU Complications Acute Respiratory Distress Syndrome ( ) Gastrointestinal Bleed ( ) Medications Continuous Infusion Neuromuscular Blocking Agent < ( ) Steroid Use While on Ventilator ( ) Haloperidol Use While on Ventilator ( ) Haloperidol Use in ICU ( ) Aminoglycoside Use in ICU ( ) Nutrition After ICU Admission Enteral Feeding < ( ) Parental Nutrition < ( ) Transfusion Needs After ICU Admission Received Red Blood Cells in First 48 ICU ( ) Receiving Red Blood Cells in ICU < ( ) * Variables are described in detail in the Supplementary Appendix Methods E14