OUTCOMES RESEARCH
Providing the evidence for evidence-based medicine©
Infection Prevention
Prophylactic Antibiotics
Supplemental Oxygen
Normothermia
Normoglycemia
Smoking
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Surgical Site Infections
Common
• >500,000 surgical site infections per year in the States
• 1-3% incidence overall; ≈10% after colon surgery
Serious
• Increases hospital duration ≈1 week
• Doubles ICU admission and mortality
Costly
• $1.6 billion annually in the United States
• 3.7 million excess hospital days yearly in the States
CMS priority
• Probable “pay-for-performance” measure
Decisive Period
All wounds become contaminated
Infections established within 2 h of contamination
• Interventions most effective during “Decisive Period”
Progression to infection determined by
• Prophylactic antibiotics
• Host defense
Prophylactic Antibiotics
Effective only during the decisive period
• Subsequent administration useless (or harmful)
Should be given within 1 hour before incision
• Repeat after 4-6 hours for long operations
• Discontinue within 24-48 hours
Various guidelines for type of antibiotic
• In practice, surgeons choose antibiotics
• Our mission is to give them — on time
Host Defense
Oxidative killing by neutrophils
• Primary defense against surgical pathogens
Oxygen is transformed to superoxide radical
– Killing determined by tissue oxygen
Measuring Tissue Oxygen
Tissue oxygenation ≠ saturation; much lower than arterial PO2
Tissue Oxygen Correlates with Infection
O b s e rv e d - E x p e c te d
In fe c tio n R a te (% )
20
10
0
-1 0
45
55
65
P s q O 2
75
(m m
85
95
H g )
Hopf, et al., 1996, Arch Surg
Supplemental Oxygen
Supplemental Oxygen
• Easy to provide
• Inexpensive (a few cents/patient)
Recent utilization
• Usually 30% in Europe
• Essentially random concentrations in the States
Rationale for various concentrations unclear
Atelectasis: Pulmonary Function
30%
80%
14
16
AaDO2 (mmHg)
29 ± 13
30 ± 8
0.73
Saturation (%)
95 ± 2
95 ± 2
0.45
Number
P
Akça, et al. 1999, Anesthesiology
Postoperative Atelectasis
10
8
6
Atelectasis
4
(%)
2
These data provide a
99% power to detect a
2% difference in the
atelectasis rate, at an
alpha level of 0.05
0
30
80
FiO2 (%)
Hemodynamic Effects
40%
100%
1860
2300
CI
2.8
2.5
MAP
69
69
SVR
Harten, et al 2005, JCVTA
Greif, et al. NEJM, 2000
Hypothesis: 80% O2 reduces wound infection risk
500 patients having elective colon resection
• Standardized antibiotic, anesthetic, & fluid management
• Intraoperative core temperature maintained at 36oC
Randomization
• 30% oxygen (balance nitrogen); PaO2 ≈ 120
• 80% oxygen (balance nitrogen) ; PaO2 ≈ 350
Wound infections
• Wounds evaluated daily by a blinded observer
• Pus and positive culture required for diagnosis
Subcutaneous Oxygen Tension (n=30)
200
PsqO2
(mmHg)
150
80% FiO2
100
30% FiO2
50
0
Intra-op
1
2
3
Post-op
4 0 1
Time (h)
2
3
Surgical Wound Infections (n=500)
Hospitalization
(days)
Infection (%)
30% Oxygen
80% Oxygen
P
11.9 ± 4
12.2 ± 6.1
0.26
11
5
0.01
Oxygen is as effective as antibiotics!
Effect of Infections
Number
Hospitalization
(days)
Infected
Uninfected
40
460
18 ± 9
11 ± 4
P
<0.001
Infections prolong hospitaliation by a full week
Pryor, et al. JAMA, 2004
Protocol
• 160 patients randomized to 35% or 80% oxygen
– 30% at low risk of infection
– Inadequate sample size; stopped early
• Anesthetic, fluid, and pain management uncontrolled
• Unblinded, retrospective evaluation of wound infection
Results
• Five patients dropped from 80% oxygen group
• Patients assigned to 80% oxygen were
– Twice as likely to have BMI >30 kg/m2
– Lost more blood, received more fluid
– More likely to require postoperative intubation (5 vs. 1 pt)
• 80% oxygen increased infection risk from 11% to 25%
Belda, et al. 2005, JAMA
Standardized antibiotic, anesthetic, & fluid management
Randomization
• 30% vs. 80% oxygen (balance nitrogen)
Wound infections: CDC criteria by blinded observer
Hospitalization
(days)
Infection (%)
30% Oxygen
80% Oxygen
P
10.5 ± 4.4
11.7 ± 7.0
0.09
35
22
0.04
Adjusted odds ratio 0.46 (95 CI 0.22-0.95, P = 0.04)
Additional Evidence
Myles, et al.
(n = 2,000)
Infection
(%)
Fleischmann,
et al. (n = 418)
Infection
(%)
80% Oxygen,
20% Nitrogen
70% Nitrous,
30% Oxygen
P
7.7
10.0
0.03
65% Nitrous,
35% Oxygen
65% Nitrogen,
35% Oxgyen
20
15
0.21
Temperature and Infection
Hypothermia
• Decreases tissue oxygen
• Impairs numerous immune functions
Hypothesis: normothermia reduces infection risk
200 patients having elective colon resection
• Standardized antibiotic, anesthetic, & fluid management
• Randomized to normothermia or ≈2°C hypothermia
Wound infections
• Wounds evaluated daily by a blinded observer
• Pus and positive culture required for diagnosis
Kurz, et al., 1996, NEJM
N o rm o the rm ic Hyp o the rm ic
P
Te m p e rature
36.6 ± 0.5
34.7 ± 0.6
<0.001
Infe ctio ns (%)
6
19
<0.01
12.1 ± 4.4
14.7 ± 6.5
=0.001
Ho s p italizatio n
(d ays )
(n = 200)
Normothermia is more effective than antibiotics!
Beneficial effect of active warming on infection
confirmed by Melling, et al. Lancet, 2001
Forced-Air vs. Circulating-Water
38
Forced-Air
36
3.5°C
T em p
(°C) 3 4
Circulating-Water
0
4
8
Time (h)
12
Kurz, et al. 1993, Anesth Analg
Fluid Warming
Cooling by intravenous fluids
• 0.25°C per liter crystalloid at ambient temperature
• 0.25°C per unit of blood from refrigerator
Cooling prevented by warming solutions
• Type of warmer usually unimportant
Fluid warming does not prevent hypothermia!
• Most core cooling from redistribution
• 90% of heat loss is from anterior skin surface
Smoking Decreases Tissue Oxygen
Tissue oxygen decreases: 65 ± 7 to 44 ± 3 mmHg
• Jensen, et al. Arch Surg, 1991
Tissue oxygen 40-50 mmHg —> infection
• Hopf, et al. Arch Surg, 1997
"Pack-a-day" smokers hypoxic most of the time
Hypothesis: smoking
• Increases the risk of surgical wound infection
Subjects: 200 patients having colon resection
Smoking and Infection (1996)
N
Infections (%)
Hospital Duration (days)
Smokers
Nonsmokers
76
148
22%
7%
<0.001
15 ± 7
13 ± 5
0.02
P
Kurz et al., 1996, NEJM
Smoking and Infection (≥2000)
Greif, et al., 2000, NEJM, n=500
• No effect of smoking on infection risk
Fleischmann, et al., 2005, Lancet, n=400
• No effect of smoking on infection risk
Belda, et al., 2005, JAMA, n=300
• No effect of smoking on infection risk
Conclusion
• No effect of smoking on infection now…
• Because smoking is no longer allowed in hospitals
Hyperglycemia and Infection
Tight control of glucose improves immunity
– [Gallacher et al. Diabet Med 1995]
Glucose control maintains neutrophil phagocytosis
– [Athos et al. Anesth Analg 1999]
Mortality reduced by intensive insulin therapy in
critical care patients (including cardiac surgery)
– [Van Den Berghe et al., N Engl J Med 2001]
Summary
Prophylactic antibiotics:
• Most effective when given within one hour before incision
Supplemental oxygen:
• Does not cause atelectasis
• Halves the risk of surgical wound infection
Maintaining perioperative normothermia:
• Reduces the risk of surgical wound infection 3-fold
• Reduces the duration of hospitalization 20%
Smoking:
• No longer increases infection risk
• Many other harmful effects
Hyperglycemia:
• Importance of intraoperative glucose control remains unknown
Recommendations
Timely antibiotic administration
Provide 80% oxygen when practical
Maintain Normothermia
• Forced-air
• Fluid warming
Euglycemia
• Probably prudent
OUTCOMES RESEARCH
Providing the evidence for evidence-based medicine©