Daily interruption of sedative infusions and complications of critical illness in mechanically ventilated patients

1. Daily interruption of sedative infusions and complications of critical illness in mechanically ventilated patients Critical Care Med 2004 Vol.32 No.6 R3 曾耀賢

2. Critical patients /c MV: frequent require sedation and analgesia • BZD, propofol and Haldol for sedation • Opiates for analgesia • However, the strategies of these drugs are variable • Developed protocol to minimize detrimental effects of overdose or accumulation • Daily interruption of continuous sedation • Daily interruption until patients was awake • Reduction of average duration of MV: 2.4 days • Reduction in average ICU length of stay: 3.5 days

3. Daily interruption of sedation • MV and critical illness: more easy to cause nosocomial complications (VAP) • Long duration of MV & ICU LOS: more complications of critical illness • Seven complications: • Ventilator-associated pneumonia • Upper gastrointestinal hemorrhage • Bactremia • Barotrauma • Venous thromboembolic disease • Cholestasis • Sinusitis Determine whether the strategy was associated with a reduction in these complications

4. Methods • Patients and Study Design • From database of our previous published, prospective, randomized-controlled study • 128 patients database: provided to investigator to evaluate and ensure accurate assignment • Investigator were not involved in original study; no documentation of study was present; all charts were reviewed independently

5. Methods • Data Collection and Definition of Variables • Demographic data • Age, gender, BW, Acute physiology & chronic healthy evaluation II severity of illness score • Use of a ventilator strategy utilizing permissive hypercapnia • Hypoventilation to allow Pco2 ≧ 50mmHg • ICU LOS • Duration of mechanical ventilation

6. Methods • Data Collection and Definition of Variables • To establish the presence of the identified seven complications associated with MV & clinical illness • Predefined clinical criteria • Complications were selected based on • Clinical importance • Frequency • Reliability of disclosure from a retrospective chart review • Complications: required to be new & distinct

7. Methods • Data Collection and Definition of Variables • Ventilation associated pneumonia: • new lung opacity, • ≧2 criteria (BT <36 or >38℃; WBC <4K or >10K; purulent secretion) • UGI bleeding: • confirm by UE; mesenteric angiography; • combination of grossly visualized blood from NG and subsequent blood transfusion

8. Methods • Data Collection and Definition of Variables • Bacteremia: • positive blood culture; • positive of CNS required serial demonstration • Barotrauma: • pneumothorax requiring chest tube insertion • Venous thromboembolic disease • Venous thrombosis by Doppler, venography, infused CT

9. Methods • Data Collection and Definition of Variables • Pulmonary embolus • Proven by pulmonary angiogram, infused spiral CT • Cholestasis • Elevated ALKP, Bil T; imaging study; need for procedural intervention • Sinusitis • Gross purulence from nares or sinus fluid present • Sinus CT scan and subsequent endoscopic drainage

10. Methods • Data Collection and Definition of Variables • Deep venous thrombosis prophylaxis was defined as • Daily administration of subcutaneous unfractionated or LMWH or • Intermittent pneumatic compression devices for period ≧75% of time spent in the ICU • Stress ulcer prophylaxis was defined as • Daily PPI, H2 blocker or sucralfate for period ≧75% of time spent in the ICU

11. Results • 126 patients had medical records available • 66 patients in the sedative interruption group • 60 patients in the control group

12. Results

13. Results • Similar in the two groups • Demographic characteristic • Acute physiology and chronic healthy evaluation II scores • Frequency of use of permissive hypercapnia ventilation strategy

14. Results • Incidence of prophylaxis is similar • Deep venous thrombosis prophylaxis • 90.2 % in daily sedation interruption group • 92.5 % in the control group • p = 1.0 • Gastric stress ulcer prophylaxis • 90.5 % in daily sedation interruption group • 96.3 % in the control group • p = 1.0

15. Results • Outcome • After blinded assessment for all complications • Sedative interruption group experienced • 13 complications in 12 patients (2.8%) • Control group experienced • 26 complications in 19 patients (6.2%) • p = 0.04 (generalized estimating equation)

16. Results • Outcome • Six of the seven complications occurred more frequently in control group

17. Results • Kaplan-Meier analysis of time from intubation or from ICU admission to first complication

18. Results

19. Discussion • Pain and anxiety are common among patients in ICU, it may be attributed to • Discomfort of procedures (intubation, MV) • Isolation from familiar surroundings • Lack of control or autonomy • Uncertainty regarding prognosis

20. Discussion • Sedatives and analgesics are frequently administered during MV • Alleviate pain and anxiety • Decrease excessive oxygen consumption • Facilitate nursing care • So, bedside nursing role of careful monitoring of sedatives and analgesia in extremely important

21. Discussion • The use of sedation protocols mandating daily interruption of continuous infusions or a nursing-directed protocol targeting • Reduction in sedative dosing  shorten duration of MV & ICU LOS • Such reductions in sedation without increasing adverse events (removal of ETT or CVP)

22. Discussion • Determine whether a protocol of daily interruption of sedative infusion affect incidence of common complications • Complications are routinely studied individually • study complications in aggregate  create a risk of possible interrelationship not immediately recognized • Comparison between groups was analyzed using the general estimating equation • Permits comparisons of the sum of complications while accounting for the possibility of interrelationships between multiple complications among individual patients

23. Discussion • Kaplan-Meier curves: data for the time to first complication • Disparity later in the ICU course  more ICU time, more increase the chance of complication • Unlike general estimating equation: evaluate the sum of all complications & potential interrelationship • K-M curve evaluate only the first complication in each patient  No differences between these two group

24. Discussion • Some complications (VAP) have been clearly linked to duration of MV • Cook et al.: cumulative risk of VAP increase over time, risk of VAP per day • 3.3% at MV day 52.3% at day 101.3% at day 15 • Bacteremia: associated with venous catheters • More present when intubation and MV • Understandable if higher rate in control group

25. Discussion • Critical patients are frequent immobilized • Subjected to procedures involving invasive instrument • More venous thromboembolic events, even prophylaxis • At least 4 complications: direct result of invasive instrumentation • Bacteremia (venous catheters) • Shorten duration of MV & ICU LOS  reduce the need and duration of venous catheter placement • VAP (endotracheal intubation)

26. Discussion • At least 4 complications: direct result of invasive instrumentation • Barotrauma • Reducing intubation time  reduce incidence? • Lacking convincing data to support • Iatrogenic pneumothorax during central catheter placement • NG and supine positioning  sinusitis  Shortening ventilator and ICU time  decrease the need for these invasive devices

27. Discussion • This study has limitations worth nothing • Described complications were not prospectively defined and followed in the original investigation • To minimized bias • Database was reviewed blinded • Investigators had never seen the database before this study • Didn’t prospectively seek to identify complications in the original study • Possible some were undetected • However, potential difference in incidence of undetected complications seed unlikely

28. Discussion • Many of complications are routinely sought, or • Only identified by the need for an intervention • Barotrauma leading to chest tube placement • Cholecystitis or sinusitis leading to surgery • Further reducing the likelihood of underrecognition of these complications • Retrospective evaluation based on medical chart • Inherent limitations • in CVP manipulation or MV setting: not reliably

29. Conclusion • Common complications of critical illness reduce • when intubated, mechanically ventilated patients by protocol of daily sedative interruption • Improved outcomes are likely the result of reduced duration of MV and ICU LOS