Anesthesie en Outcome na Majeure Abdominale Heelkunde
Kan het peroperatieve anesthesiebeleid tijdens majeure (niet-vasculaire)
abdominale heelkunde de postoperatieve outcome beïnvloeden?
M. Verhaegen
Vrijdagochtendkrans 05-09-2008
Postoperative Morbidity and Mortality and the Surgical Procedure
Vascular surgery Myocardial infarction
Total hip or knee replacement Pulmonary embolism
Thoracic or upper abdominal surgery Pneumonia
Major Abdominal Surgery (MAS):Postoperative Morbidity
Pulmonary complications Cardiovascular complications Prolonged ileus Anastomotic leaks
Fistulae Peritonitis
Surgical wound infections Colon surgery: 10 – 30 % Prolonged hospitalization (5 – 20 days) Increased cost
Nausea and vomiting Pain
Anesthesia for MAS
Induction of anesthesia Anesthetic technique Intraoperative fluid management Optimal perioperative oxygen concentration Muscle relaxation / antagonism Blood transfusion Body temperature Postoperative analgesia
Surgery, Anesthesia and Outcome
Patient safety Mortality Major morbidity
Patient satisfaction Minor morbidity Side effects
Economic benefits
Surgery, Anesthesia and Outcome
Patient safety Mortality
Major morbidity Patient satisfaction
Minor morbidity Side effects
Economic benefits
Mortality rate contribution
Patient 1 in 870
Surgery 1 in 2860
Anesthesia 1 in 185 256
Confidential enquiry into perioperative deaths (Lancet 1987)
Major Abdominal Surgery (MAS) and
Epidural Anesthesia and Analgesia (EAA):
What are the benefits?
MAS and EAA: Postoperative Effects (1)
Epidural analgesia provides superior postoperative analgesia Local anesthetic ± opioid compared to systemic opioids For up to 72 h postoperatively Especially during movement, coughing Part of multimodal postoperative rehabilitation programmes
Improved exercise capacity and vitality for 6 w postoperatively Faster recovery of bowel function
Thoracic epidural with local anesthetics lasting > 24 h, compared to postoperative analgesia with systemic opioids
No increased incidence of anastomotic leaks
Meta-analysis of 16 prospective RCTs (1985-2005) comparing postoperative epidural analgesia and parenteral opioid analgesia after colorectal surgery
EA: Epidural analgesia (local anesthetic ± opioid): n = 406 Control: Parenteral (non)opioid analgesia: n = 400
Primary outcome: length of hospital stay Secondary outcomes
Postoperative pain (VAS score at 24 and 48 h) Recovery of bowel function Anastomotic leakage Cardiac complications Respiratory complications Nausea and vomiting Sedation Pruritus Urinary retention Hypotension
Marret et al., Br J Surg (2007); 94: 665-73
Marret et al., Br J Surg (2007; 94: 665-73
Marret et al., Br J Surg (2007; 94: 665-73
Epidural Control
VAS at 24 h (mmHg) 12 18
VAS at 48 h (mmHg) 27 33
Duration of ileus - 36 h
Urinary retention 10 % 1 %
Pruritus 21 % 5 %
Hypotension 10 % 0 %
MAS and EAA: Postoperative Effects (2)
No reduction of postoperative mortality No reduction of major postoperative morbidity
Inconsistent results of many RCTs Meta-analyses
Meta-analysis of RTCs Randomisation to intraoperative neuraxial blockade or not
141 trials (1971-1995) 9559 patients (NB: 4871, no NB: 4688)
Outcome measures Mortality Morbidity
Neuraxial blockade Reduction of overall mortality by 1/3 Reduction of major morbidity by 40 – 60 %
Deep vein thrombosis Pulmonary embolism Perioperative blood loss Postoperative blood loss requiring transfusion Pneumonia Respiratory depression Renal failure
CORTRA, Rodgers et al., Br Med J (2000); 321: 1-12
Remarks General anesthesia or neuraxial anesthesia
Effect of avoidance of general anesthesia? LMWH is now more commonly used Improved surgical and anesthetic techniques Improved diagnostic techniques
Pulmonary atelectasis CT scan > chest X-ray
Myocardial damage Troponin Ic
CORTRA, Rodgers et al., Br Med J (2000); 321: 1-12
Meta-analyses of 65 RTCs (1966-1995) Significantly reduced incidence of atalectasis with epidural
opioids compared to systemic opioids 11 trials (1975-1995) Abdominal and thoracic surgery 769 patients
Significantly reduced the incidence of pulmonary infection or pulmonary complications in general with epidural local anesthetics
Pulmonary infection: 5 trials (1971-1987), n = 215 Pulmonary complications: 6 trials (1974-1987), n = 247
Ballantyne et al., Anesth Analg (1998); 86: 598-612
MAS and EAA: Postoperative Effects (2)
No reduction of postoperative mortality No reduction of major postoperative morbidity
Inconsistent results of many RCTs Meta-analyses: problems
Older studies, not relevant to present-day practices, included Excessive heterogeneity (oversimplification of complex issues) Publication bias: tendency to publish only positive results Difficult quality assessment Definition of endpoints
Ballantyne et al., J Clin Anesth (2005); 17: 382-91
MAS and EAA: Postoperative Effects (2)
No reduction of postoperative mortality No reduction of major postoperative morbidity
Inconsistent results Meta-analyses Studies investigating major abdominal surgery do not support
an effect on major morbidity Lack of power?
Multicentre trial (15) 1021 patients
Intraabdominal surgery Aortic (37 %), gastric, biliary or colon
Randomised to 1 of 2 groups Control: general anesth. + postoperative iv or im opioids
(PCA) (n = 507) General / epidural anesth. (local anesthetic ± morphine) +
postoperative epidural analgesia (morphine) (n = 514) Primary endpoints
Death within 30 days Major postsurgical morbidity within 30 days
Major cardiac, pulmonary, cerebrovascular or renal complications
Park et al., Ann Surg (2001); 234: 560-71
Significantly better postoperative pain control in the epidural group
No significant difference in overall physical performance (7 d) No significant difference in 30 day mortality
Control Epidural P value
All patients (n = 507 / 514) 3.3 % 3.9 % 0.74
Aortic (n = 190 / 184) 2.6 % 2.2 % 0.96
Nonaortic (n = 317 / 330) 3.8 % 4.8 % 0.64
Park et al., Ann Surg (2001); 234: 560-71
Overall, no significant difference in major complications Nonaortic surgery: no significant difference Aortic surgery
Decreased incidence of myocardial infarction, respiratory failure, and stroke
Epidural patients were extubated 13 h earlier (p = 0.01)
Control Epidural P value
All patients (n = 507 / 514) 22 % 17 % 0.11
Nonaortic (n = 317 / 330) 13 % 15 % 0.42
Aortic (n = 190 / 184) 37 % 22 % < 0.01
New myocardial infarction 7.9 % 2.7 % 0.05
Respiratory failure 28 % 14 % < 0.01
New stroke 4.7 % 0.5 % 0.03
Park et al., Ann Surg (2001); 234: 560-71
Multicentre (25 hospitals, 6 countries) 915 high-risk patients (at least 1 of 9 comorbid states)
Major abdominal or thoracic surgery Elective, non-laparoscopic, lasting > 1 h No cardiac or pulmonary procedures
Randomised to 1 of 2 groups Control: general anesth. + postoperative iv opioids (PCA)
and NSAIDs (n = 441) General / epidural anesthesia + postoperative epidural
analgesia (72 h, local anesthetic + opioid) (n = 447) Primary endpoints
Death within 30 days Major postsurgical morbidity
Rigg et al., Lancet (2002); 359
Rigg et al., Lancet (2002); 359No significant differences in allocation
Procedure n
Esophagectomy 18
Non-laparoscopic gastric surgery 72
Non-laparoscopic biliary surgery 77
Pancreatic surgery 35
Bowel surgery 364
Major surgery for ovarian cancer 23
Surgery for aortic aneurysm 142
Aorto-femoral bypass-graft surgery 28
Renal tract surgery 59
Bladder surgery 12
Prostate surgery 7
Radical hysterectomy 44
Pelvic exenteration 2
Other 36
Rigg et al., Lancet (2002); 359
No significant differences in allocation
Procedure n
Esophagectomy 18
Non-laparoscopic gastric surgery 72
Non-laparoscopic biliary surgery 77
Pancreatic surgery 35
Bowel surgery 364
Major surgery for ovarian cancer 23
Surgery for aortic aneurysm 142
Aorto-femoral bypass-graft surgery 28
Renal tract surgery 59
Bladder surgery 12
Prostate surgery 7
Radical hysterectomy 44
Pelvic exenteration 2
Other 36
71.3%
No significant differences in allocation
Epidural analgesia was associated with lower pain scores during the first 3 postoperative days
No significant difference in mortality at 30 days Control group: 4.3 % Epidural group: 5.1 %
No overall difference in major postoperative morbidity Patients who had at least one morbid endpoint: 60.5 % in the
control group vs 56.6 % in the epidural group (p = 0.26) Only respiratory failure occurred less frequently in patients
managed with epidural techniques: 23.3 % vs 30.2 % (p = 0.02)
Rigg et al., Lancet (2002); 359
Selected number of predetermined subgroup analyses of Rigg et al. trial:• Increased risk of respiratory complications• Increased risk of cardiac complications• Aortic surgery
Respiratory failure = Need for ventilation > 1 h after surgery, or reintubation of PaO2 ≤ 50 mmHg or PaCO2 ≥ 50 mmHg on room air
Peyton et al., Anesth Analg (2003); 96: 548-54
The only significant difference between epidural and control groups was respiratory failure.
70 ASA I or II patients > 70 y Mean age approximately 76 y for both groups
Elective major abdominal (cancer) surgery Randomly assigned to
General / epidural anesthesia + postoperative epidural analgesia (local anesthetic + opioid) (n = 35)
General anesthesia + postoperative iv PCA (morphine) (n = 35) Endpoints
Pain intensity (VAS score) Mental status Patients satisfaction score Cardiac function Respiratory function Gastrointestinal function
Mann et al., Anesthesiology (2000); 92: 433-41
Pain relief was significantly better during 5 postoperative days in the epidural group, at rest and after coughing
Mental status scores were significantly better on postoperative days 4 and 5 in the epidural group (although, for each day only once out of two daily measurements)
The incidence of postoperative delirium was similar in both groups
Bowel function recovered faster in the epidural group Cardiopulmonary complications were similar in both groups
Mann et al., Anesthesiology (2000); 92: 433-41
MAS and EAA: Postoperative Effects (3)
Recently: Positive effect on long-term survival after cancer surgery?
Intraoperative general anesthesia + epidural anesthesia/analgesia
MAS and EAA: Postoperative Effects (3)
Recently: Positive effect on long-term survival after cancer surgery?
Side effects and complications Pruritus (epidural opioids) Urinary retention Low incidence of severe complications if contraindications are
respected Epidural hematoma Epidural abcess Neurologic injury (temporary, permanent)
MAS and EAA:Conclusions (1)
EAA for MAS consistently results in superior postoperative analgesia and improved recovery of bowel function
There is insufficient evidence that EAA for MAS affects mortality and major postoperative morbidity
EAA techniques are associated with minor side effects
Major complications due to EAA are rare if contraindications are heeded
Surgery, Anesthesia and Outcome
Patient safety Mortality Major morbidity
Patient satisfaction Minor morbidity Side effects
Economic benefits
MAS and EAA:Conclusions (2)
Epidural anesthesia/analgesia for major abdominal surgery has is important in terms of patient-oriented outcomes and patient satisfaction
However, since an effect of epidural anesthesia/analgesia on mortality and major morbidity after major abdominal surgery remains unproven, the prevention of severe complications of neuraxial techniques is absolutely indicated
Is mild hypothermia clinically important?
Anesthesia and Hypothermia
Anesthesia-related thermoregulatory impairment Initially: internal core to peripheral redistribution of body heat Subsequently: heat loss exceeding metabolic heat production
Inadvertent perioperative hypothermia: core body temperature ≤ 36.0 °C
Incidence ≈ 20 %? Poor compliance to guidelines
Mistaken belief that forced air warming increases risk of infection Surgeons’ complaint of discomfort Inconsistent monitoring Inadequate knowledge of the consequences
Hypothermia and Perioperative Complications (1)
Increased blood loss and transfusion requirement Coagulopathy
Impaired platelet function Impaired function of enzymes of the coagulation cascade
Rajagopalan et al., Anesthesiology (2008); 108: 71-7
15 prospective RCTs (1966-2006) comparing normothermic patients with patients who had mild (34-36 °C) intraoperative hypothermia
14 reporting blood loss (1219 patients) 10 reporting transfusion requirements (985 patients)
Median (quartiles) of the mean temperatures reported in the blood loss trials
Normothermic: 36.6 °C (36.4 °C, 36.7 °C) Hypothermic: 35.6 °C (35.4 °C, 35.8 °C)
Significant variability among studies Blood loss: estimated 16 % lower average blood loss for
normothermic vs hypothermic patients (P = 0.009) Transfusion: normothermia is associated with 22 % less risk
of transfusion than hypothermia (P = 0.027)
Rajagopalan et al., Anesthesiology (2008); 108: 71-7
Rajagopalan et al., Anesthesiology (2008); 108: 71-7
Rajagopalan et al., Anesthesiology (2008); 108: 71-7
Blood loss: estimated 16 % lower average for normothermic vs hypothermic patients
Rajagopalan et al., Anesthesiology (2008); 108: 71-7
Transfusion: normothermia is associated with 22 % less risk than hypothermia
Hypothermia and Perioperative Complications (2)
Increased blood loss and transfusion requirement Surgical wound infection
Vasoconstriction with impaired subcutaneous oxygen tension Neutrophils: impaired oxidative killing Reduced deposition of collagen
Impaired immune function
Double blinded RCT 200 patients Colorectal surgery
All patients: cefamandole, metronidazole Randomy assigned to
Hypothermia: routine intraoperative thermal care (n = 96) Normothermia: additional warming (n = 104)
Warmed fluids, farced air warming Daily wound inspection by surgeons until discharge and
after 2 weeks Culture-positive pus = infected
Patient characteristics were similar for the 2 groups
Kurz et al., NEJM (1996); 334: 1209-15
Kurz et al., NEJM (1996); 334: 1209-15
Kurz et al., NEJM (1996); 334: 1209-15
Intraoperative core temperatures approximately 2 °C below normal during colorectal surgery: triple the incidence of wound infection and prolong hospitalization by about 20 %.
X 3
+ 20 %
Hypothermia and Perioperative Complications (3)
Cardiac complications Prolonged recovery Prolonged hospitalization Negative nitrogen balance Patient discomfort
Perioperative Maintenance of Normothermia Reduces the Incidence of Morbid Cardiac Events.
Frank et al., JAMA (1997); 277: 1127-34
RCT comparing routine thermal care (hypothermia) to additional warming care (normothermia)
300 patients with coronary artery disease or at high risk for coronary disease
Surgery: abdominal, thoracic, or vascular Cardiac events
Unstable angina Ischemia Cardiac arrest Myocardial infarction
Hypothermia was an independent predictor of morbid cardiac events: there was approxiamtely 55 % reduction in risk if normothermia was maintained
Postoperative ventricular tachycardia occurred less frequently in the normothermic group than in the hypothermic group
Frank et al., JAMA (1997); 277: 1127-34
Normothermia Hypothermia P-value
Core temperature after surgery (mean)
36.7 35.4 < 0.001
Incidence of morbid cardiac events
1.4 % 6.3 % 0.02
Postoperative ventricular tachycardia
2.4 % 7.9 % 0.04
Mild Intraoperative Hypothermia: Conclusion
Even mild inadvertent intraoperative hypothermiashould be avoided
Intraoperative supplemental oxygen administration:
Is there an optimal concentration?
Perioperative Supplemental Oxygen Concentration
Preoxygenation FiO2 1.0: development of (mild) atelectasis is a consistent
finding And we do this every day…
FiO2 0.8: minimal atelectasis Significantly faster desaturation compared with 100 % O2
Intraoperative inspired oxygen concentration Postoperative supplemental oxygen administration
Does every patient need it? How much? For how long? Hemodynamic benefits? Clinical significance?
Edmark et al., Anesthsiology (2003); 98: 28-33
Intraoperative High FiO2: Risks (1)
Resorption atelectasis Airway obstruction: absorption of trapped gas
Even after a few breaths of 100 % oxygen Reversible with positive pressure
No airway obstruction: if VA/Q is low, absorption of oxygen into the capillaries may exceeding the inspired gas flow
After longer duration of exposure?
Benoit et al., Anesth Analg (2002); 95: 1777-81
Intraoperative High FiO2: Risks (2)
Ischemic reperfusion injury Free radical damage Mainly animal studies, no large RCT in humans
Oxygen toxicity Prolonged exposure
FiO2 0.8 < 24 h: safe?
FiO2 1.0 at 1 atm for 6 d: irreversible damage
Pulmonary intersitital edema Pulmonary fibrosis
Intraoperative High FiO2: Benefits (1)
Reduced incidence of wound infection? Yes
Greif et al., N Engl J Med (2000); 342: 161-7 Sessler and Akca, Clin Infect Dis (2002); 35: 1397-404 Belda et al., JAMA (2005); 294; 2035-2042
No Pryor et al., JAMA (2004); 291: 79-87
(Retrospective, underpowered?, treatment groups were not homogenous, variables possibly increasinf infection risk were not controlled)
Surgical Wound Infection and Oxygen
Wounds are hypoxic compared to normal tissue due to a disrupted vascular supply (injury, vessel thrombosis)
Resistance to infection depends on wound PO2
Oxidative killing by neutrophiles Wound tissue PO2 predicts the risk of wound infection in
surgical patients Oxygen is important for tissue repair and wound healing
Collagen synthesis is PO2-dependent Oxygen is a cell signal interacting with growth factors
Greif et al., NEJM (2000); 342: 161-7
Intraoperative High FiO2: Benefits (2)
Reduced incidence of nausea and vomiting? Controversial clinical data
Yes Greif et al., Anesthesiology (1999); 91: 1246-52 (colorectal surgery) Goll et al., Anesth Analg (2001); 92: 112-17 (gynecological laparoscopy)
No Purhonen et al., Anesth Analg (2003); 96: 91-6 (ambulatory gynecological
laparoscopy) Joris et al., Br J Anaesth (2003); 91: 857-61 (thyroidectomy) Treschan et al., Anesthesiology (2005); 103: 6-10
Gastrointestinal ischemia (abdominal surgery) Dopamine release from carotid bodies is inversely related to
blood PO2
?Is there an optimal intraoperative FiO2?
Intraoperative FiO2 0.8 may reduce the incidence of postoperative wound infections
High intraoperative FiO2 is not a reliable treatment to reduce postoperative nausea and vomiting
The risks of intraoperative high inspired oxygen concentrations are not clear
We need data evaluating more moderate oxygen concentrations
Optimal Intraoperative FiO2: Conclusions