Enhanced Recovery After Surgery The ERAS protocol Prof. Ioana Grigoraș Anesthesia and Intensive Care Department University of Medicine and Pharmacy, Gr.T.Popa Regional Institute of Oncology Iasi, Romania

Factors influencing patient recovery Accelerated recovery Pre-op information Optimised organ function No nutritional defects No alcohol pre-op Stop smoking pre-op Neuraxial blockade Minimally invasive surgery Normothermia Nausea prevention Ileus prevention Early feeding Good oxygenation Good sleep Opioid sparing Evidence-based post-op care Anxiety, fear Pre-op organ dysfunction Surgical stress response Hypothermia Nausea, vomiting Ileus Semi-starvation Hypoxaemia Poor sleep Drains & tubes Catheters Delayed recovery Enhancing Recovery after GI surgery

What is ERAS ? Standardized protocol for perioperative care Multi-modal intervention Reduce operative stress Support organ function Reduced morbidity Accelerate convalescence Functional capacity Days Weeks Modificarile perioperatorii ale capacitatii functionale Interventia multimodala – analgezie, nutritie enterala, strategii de reducere a stresului perioperator, mobilizare – care va controla fiziologia postoperatorie are ca si consecinta reducerea morbiditatii si accelerarea convalescentei. Traditional Care Enhanced Recovery Henrik Kehlet, Br J Anaesth 1997; 78 : 606

What is ERAS ? Standardized protocol for perioperative care Multi-modal intervention preop information stress attenuation pain relief exercise enteral nutrition nurses surgeons anesthesists dietician kinesitherapist Modificarile perioperatorii ale capacitatii functionale Interventia multimodala – analgezie, nutritie enterala, strategii de reducere a stresului perioperator, mobilizare – care va controla fiziologia postoperatorie are ca si consecinta reducerea morbiditatii si accelerarea convalescentei. Multi-disciplinary approach Henrik Kehlet, Br J Anaesth 1997; 78 : 606

Early removal of catheters/drains Epidural Anaesthesia Peri-op fluid management Remifentanyl No premed DVT prophylaxis Pre-op councelling No bowel prep Early mobilisation CHO-loading/ no fasting ERAS Perioperative nutrition Incisions Bairhugger No NG tubes Prevention of ileus/ prokinetics Early removal of catheters/drains Oral analgesics/ NSAID’s Lassen et al, Arch Surg, 2009

Outline Anesthetist approach Surgeon approach Protocolization

Outline Anesthetist approach Surgeon approach Protocolization

Enhanced Recovery in practice Fluid management Postoperativ glycaemic control Postoperative nutrition Early mobilisation Rapid hydration / nourishment Appropriate iv therapy Catheters removed early Regular oral analgesia Avoid opiates Referral from Primary Care Pre-Operative Admission Optimised medical conditions Nutrition Fasting time Carbohidrate drinking Pre-anesthestic medication Anti-thrombotic prophylaxis Operative Antimicrobial prophylaxis Multimodal analgesia PONV Optimal fluid therapy Hypotermia prophylaxis Post-Operative Follow-up

Preoperative ERAS components Patient information Health/medical optimisation Nutrition Fasting time Carbohidrate drinking Pre-anesthestic medication Anti-thrombotic prophylaxis U.O. Gustafsson et al. Clin Nutr 2012; 31: 783-800

Preoperative ERAS components Patient information Health/medical optimisation Nutrition Fasting time Carbohidrate drinking Pre-anesthestic medication Anti-thrombotic prophylaxis U.O. Gustafsson et al. Clin Nutr 2012; 31: 783-800

Preadmission education and counselling Patient information Preadmission education and counselling Decrease fear and anxiety Improve wound healing perioperative feeding postoperative mobilisation pain control Reduce the prevalence of complications Enhance Postoperative Recovery and Discharge Detailed information given to patients before the procedure about surgical and anaesthetic procedures may diminish fear and anxiety and enhance postoperative recovery and quicken hospital discharge.14,15 A preoperative psychological intervention, aimed at decreasing patient anxiety, may also improve wound healing and recovery after laparoscopic surgery.16,17 Personal counselling, leaflets or multimedia information containing explanations of the procedure along with tasks that the patient should be encouraged to fulfil may improve perioperative feeding, early postoperative mobilisation, pain control, and respiratory physiotherapy; and hence reduce the prevalence of complications.18e20 Ideally, the patient and a relative/care provider should meet with surgeon, anaesthetist and nurse. U.O. Gustafsson et al. Clin Nutr 2012; 31: 783-800

Preoperative ERAS components Patient information Health/medical optimisation Nutrition Fasting time Carbohidrate drinking Pre-anesthestic medication Anti-thrombotic prophylaxis U.O. Gustafsson et al. Clin Nutr 2012; 31: 783-800

Preoperative improvement of physiological function Prehab Preoperative improvement of physiological function Increasing exercise preoperatively WALK Training programs Although anaesthetic and surgical techniques have improved over the years, the incidence of serious postoperative complications has not declined greatly during recent decades. Pulmonary, cardiovascular and infectious complications still cause extended hospital stay, intensive care admittance, and risk of death for a relatively high proportion of patients recovering from surgery. Recent research has given us new tools for preventing postoperative complications by revealing the relationship between lifestyle and postoperative complications. Further, it has been shown that intervention is capable of reducing the risk of serious complications(1). A weekly alcohol intake exceeding 35 units is also associated with an increased risk of postoperative complications. Again, infections and cardiopulmonary complications are increased, as well as serious bleeding episodes. Wound healing is impaired resulting in wound and anastomotic dehiscence. In such patients, total abstinence for at least 4 weeks before surgery reduces the perioperative risk to normal levels.

Preoperative improvement of physiological function Prehab Preoperative improvement of physiological function Increasing exercise preoperatively WALK Increasing distance Increasing duration Increasing frequency Easier to implement Psychological preparation Motivation – adherence to exercise Less efficient Although anaesthetic and surgical techniques have improved over the years, the incidence of serious postoperative complications has not declined greatly during recent decades. Pulmonary, cardiovascular and infectious complications still cause extended hospital stay, intensive care admittance, and risk of death for a relatively high proportion of patients recovering from surgery. Recent research has given us new tools for preventing postoperative complications by revealing the relationship between lifestyle and postoperative complications. Further, it has been shown that intervention is capable of reducing the risk of serious complications(1). A weekly alcohol intake exceeding 35 units is also associated with an increased risk of postoperative complications. Again, infections and cardiopulmonary complications are increased, as well as serious bleeding episodes. Wound healing is impaired resulting in wound and anastomotic dehiscence. In such patients, total abstinence for at least 4 weeks before surgery reduces the perioperative risk to normal levels.

Preoperative improvement of physiological function Prehab Preoperative improvement of physiological function Increasing exercise preoperatively Training programs Although anaesthetic and surgical techniques have improved over the years, the incidence of serious postoperative complications has not declined greatly during recent decades. Pulmonary, cardiovascular and infectious complications still cause extended hospital stay, intensive care admittance, and risk of death for a relatively high proportion of patients recovering from surgery. Recent research has given us new tools for preventing postoperative complications by revealing the relationship between lifestyle and postoperative complications. Further, it has been shown that intervention is capable of reducing the risk of serious complications(1). A weekly alcohol intake exceeding 35 units is also associated with an increased risk of postoperative complications. Again, infections and cardiopulmonary complications are increased, as well as serious bleeding episodes. Wound healing is impaired resulting in wound and anastomotic dehiscence. In such patients, total abstinence for at least 4 weeks before surgery reduces the perioperative risk to normal levels.

Prehab Hulzebos EH, JAMA. 2006;296(15):1851-1857 Although anaesthetic and surgical techniques have improved over the years, the incidence of serious postoperative complications has not declined greatly during recent decades. Pulmonary, cardiovascular and infectious complications still cause extended hospital stay, intensive care admittance, and risk of death for a relatively high proportion of patients recovering from surgery. Recent research has given us new tools for preventing postoperative complications by revealing the relationship between lifestyle and postoperative complications. Further, it has been shown that intervention is capable of reducing the risk of serious complications(1). A weekly alcohol intake exceeding 35 units is also associated with an increased risk of postoperative complications. Again, infections and cardiopulmonary complications are increased, as well as serious bleeding episodes. Wound healing is impaired resulting in wound and anastomotic dehiscence. In such patients, total abstinence for at least 4 weeks before surgery reduces the perioperative risk to normal levels. Hulzebos EH, JAMA. 2006;296(15):1851-1857

Prehab RCT, n=279 high risk pts single centre, 2002-2005 prehospitalization period before CABG surgery may be used to improve a patient’s pulmonary condition Although anaesthetic and surgical techniques have improved over the years, the incidence of serious postoperative complications has not declined greatly during recent decades. Pulmonary, cardiovascular and infectious complications still cause extended hospital stay, intensive care admittance, and risk of death for a relatively high proportion of patients recovering from surgery. Recent research has given us new tools for preventing postoperative complications by revealing the relationship between lifestyle and postoperative complications. Further, it has been shown that intervention is capable of reducing the risk of serious complications(1). A weekly alcohol intake exceeding 35 units is also associated with an increased risk of postoperative complications. Again, infections and cardiopulmonary complications are increased, as well as serious bleeding episodes. Wound healing is impaired resulting in wound and anastomotic dehiscence. In such patients, total abstinence for at least 4 weeks before surgery reduces the perioperative risk to normal levels. Hulzebos EH et al. JAMA. 2006;296(15):1851-1857

Prehab postoperative pulmonary complication time of postoperative hospitalization Although anaesthetic and surgical techniques have improved over the years, the incidence of serious postoperative complications has not declined greatly during recent decades. Pulmonary, cardiovascular and infectious complications still cause extended hospital stay, intensive care admittance, and risk of death for a relatively high proportion of patients recovering from surgery. Recent research has given us new tools for preventing postoperative complications by revealing the relationship between lifestyle and postoperative complications. Further, it has been shown that intervention is capable of reducing the risk of serious complications(1). A weekly alcohol intake exceeding 35 units is also associated with an increased risk of postoperative complications. Again, infections and cardiopulmonary complications are increased, as well as serious bleeding episodes. Wound healing is impaired resulting in wound and anastomotic dehiscence. In such patients, total abstinence for at least 4 weeks before surgery reduces the perioperative risk to normal levels. Hulzebos EH, JAMA. 2006;296(15):1851-1857

Preoperative alcohol consumption Increase (x 3) in postoperative morbidity Cardiopulmonary complications Bleeding Wound infections Recent data have shown alcohol misusers to have a threefold increase in postoperative morbidity. Abstinence from alcohol for 1 month before surgery reduces postoperative morbidity after colorectal surgery. Mechanisms may involve reduced responses to surgical stress and improved cardiac and immune dysfunction. Withdrawal from alcohol before an operation is recommended in alcohol abusers. Alcohol abusers have a two-to-threefold increase in postoperative morbidity, the most frequent complications being bleeding, wound and cardiopulmonary complications. One month of preoperative abstinence reduces postoperative morbidity by improving organ function. Tønnesen et al. Br J Surg 1999;86:869-74

Preoperative alcohol consumption Abstinence from alcohol for 1 month before surgery reduces postoperative morbidity after colorectal surgery Recent data have shown alcohol misusers to have a threefold increase in postoperative morbidity. Abstinence from alcohol for 1 month before surgery reduces postoperative morbidity after colorectal surgery. Mechanisms may involve reduced responses to surgical stress and improved cardiac and immune dysfunction. Withdrawal from alcohol before an operation is recommended in alcohol abusers. Alcohol abusers have a two-to-threefold increase in postoperative morbidity, the most frequent complications being bleeding, wound and cardiopulmonary complications. One month of preoperative abstinence reduces postoperative morbidity by improving organ function. Does it any difference???!!??? U.O. Gustafsson et al. Clin Nutr 2012; 31: 783-800

Preoperative alcohol consumption Mean HR SpO2 Postoperative ECG and pulse oxymetry Ischemia % Recent data have shown alcohol misusers to have a threefold increase in postoperative morbidity. Abstinence from alcohol for 1 month before surgery reduces postoperative morbidity after colorectal surgery. Mechanisms may involve reduced responses to surgical stress and improved cardiac and immune dysfunction. Withdrawal from alcohol before an operation is recommended in alcohol abusers Hypoxemic episodes Arrhythmias Tønnesen et al. BMJ 1999; 318:1311–6

Preoperative alcohol consumption Mean BP Plasma noradrenaline Mean HR Plasma adrenaline Responses to surgical stress Recent data have shown alcohol misusers to have a threefold increase in postoperative morbidity. Abstinence from alcohol for 1 month before surgery reduces postoperative morbidity after colorectal surgery. Mechanisms may involve reduced responses to surgical stress and improved cardiac and immune dysfunction. Withdrawal from alcohol before an operation is recommended in alcohol abusers Serum cortisol Plasma IL-6 Plasma glucose Tønnesen et al. BMJ 1999; 318:1311–6

Preoperative alcohol consumption Alcohol consumption should be stopped 4 weeks before surgery Recent data have shown alcohol misusers to have a threefold increase in postoperative morbidity. Abstinence from alcohol for 1 month before surgery reduces postoperative morbidity after colorectal surgery. Mechanisms may involve reduced responses to surgical stress and improved cardiac and immune dysfunction. Withdrawal from alcohol before an operation is recommended in alcohol abusers. Alcohol abusers have a two-to-threefold increase in postoperative morbidity, the most frequent complications being bleeding, wound and cardiopulmonary complications. One month of preoperative abstinence reduces postoperative morbidity by improving organ function. U.O. Gustafsson et al. Clin Nutr 2012; 31: 783-800

Preoperative smoking Increased postoperative morbidity Cardiopulmonary complications Wound infections Daily smokers (>2 cigarettes daily for 1 year) have an increased risk of pulmonary and wound complications. RCTs have demonstrated reductions in the rates of both types of complications 1 month after cessation of smoking. Lindström D. et al. Ann Surg 2008, 248:739-45. Anaesthesia, 2009

Preoperative smoking Smoking cessation 4 weeks before surgery RCT n = 117 (Blinded outcome assessment) Hernia, Cholecystectomy, Hip/knee replacement Smoking cessation 4 weeks before surgery Postoperative complications 41% vs. 21% Smoking abstinent after 1 yr 33% vs. 15% Daily smokers (>2 cigarettes daily for 1 year) have an increased risk of pulmonary and wound complications. RCTs have demonstrated reductions in the rates of both types of complications 1 month after cessation of smoking. Lindström D. et al. Ann Surg 2008, 248:739-45. Anaesthesia, 2009

Preoperative smoking Meta – analysis, 11 RCTs, 1194 pts The harmful effects of tobacco smoking are well known, but its effect on surgical risk has only recently been demonstrated. The physiological effects of smoking imply changes in cardiovascular, pulmonary, immune and wound healing functions. In patients undergoing elective orthopaedic surgery, the incidence of cardiovascular complications was twice as high in smokers as in non-smokers, and clinically important infections were three times as common in smokers. An individual smoking intervention programme imposed 6- 8 weeks prior to surgery is highly effective in reducing surgical complications (2). T. Thomsen et al. Br J Surg 2009; 96: 451–461

Preoperative smoking Any complication T. Thomsen et al. Interventions for preoperative smoking cessation Cochrane Database of Systematic, 2010, 7. CD002294

Preoperative smoking Wound complications T. Thomsen et al. Interventions for preoperative smoking cessation Cochrane Database of Systematic, 2010, 7. CD002294

Smoking should be stopped 4 weeks before surgery Preoperative smoking Smoking should be stopped 4 weeks before surgery Daily smokers (>2 cigarettes daily for 1 year) have an increased risk of pulmonary and wound complications. RCTs have demonstrated reductions in the rates of both types of complications 1 month after cessation of smoking. U.O. Gustafsson et al. Clin Nutr 2012; 31: 783-800

Preoperative ERAS components Patient information Health/medical optimisation Nutrition Fasting time Carbohidrate drinking Pre-anesthestic medication Anti-thrombotic prophylaxis U.O. Gustafsson et al. Clin Nutr 2012; 31: 783-800

Bozzetti, Nutrition, 2002, 18:953

Norman, Clinical Nutrition, 2008,27, 5/15

Questions regarding perioperative nutrition: TNP vs EN ? Pre- vs post- vs pre- and postoperative ? Standard vs immunonutrition ?

ESPEN RECOMMENDATIONS Preoperative All malnourished patients All cancer patients Scheduled for upper gastro-intestinal surgery No matter the nutritional status Preoperative enteral (immuno)nutrition for 10–14 days RECOMMENDATION GRADE A

ASPEN RECOMMENDATIONS Perioperative Only moderately/severely malnourished patients scheduled for elective surgery Imposibility of meeting nutritional needs > 7-14 days Early postoperative enteral (delayed PN) nutrition

Rationale for PREOPERATIVE NUTRITIONAL SUPPORT PRO Malnourished pts → at risk of postoperative complications Reduced nutrient intake →frequent in cancer pts and correlates with nutrition status and complications Although malnutrition usually develops over weeks/months → a short course of nutrition support can improve physiologic functions Preoperative nutrition support →better tolerance for postoperative nutrition Preoperative glucose → reduced postoperative insulin resistance

Rationale for PREOPERATIVE NUTRITIONAL SUPPORT CON The nutritional status of cancer patients correlates with disease stage and cancer control If nutritional depletion is the result of metabolic use of nutrients → the benefit ?? Short-term refeeding → reversal of long-term malnutrition?? Preoperative nutrition increases the length of preoperative stay and increases the costs

Who should receive preoperative nutrition support? The patient should be moderately/severely malnutrished The procedure should be one in which nutrition support has been shown to improve outcome – thoraco-abdominal surgery Surgery should be elective and safe to delay for 7-10days The enteral route is always prefered (when possible) Combination with postoperative nutrition Immune-enhancing formulas

Preoperative nutrition Malnourished patients should receive nutritional support oral supplements enteral nutrition Immunonutrition 5 -7 days preoperatively reduce the prevalence of infectious complications in patients undergoing major open abdominal surgery In western countries, patients scheduled for PD are, in general, not malnourished, and usually present with <7% weight loss.31 In such cases, preoperative artificial nutrition is not warranted. The situation may be different in other regions. It is widely accepted that significantly malnourished patients suffer increased postoperative morbidity after major surgery.32e34 Preoperative supplements with oral sip feeds or enteral tube feeds are usually administered in these cases, but scientific evidence to support this routine (as opposed to no nutritional support) is lacking. Extrapolating data from studies in the postoperative setting suggests that parenteral nutrition should be used only if the enteral route is inaccessible. Summary and recommendation: Routine use of preoperative artificial nutrition is not warranted, but significantly malnourished patients should be optimized with oral supplements or enteral nutrition preoperatively. The role of IN has been investigated thoroughly over many years. Few studies specifically address IN for PD patients, and the variation in active immune-modulating nutrients administered makes interpretation difficult. A reduction in the prevalence of infectious complications is a consistent finding in patients with gastrointestinal cancer, as are beneficial effects on surrogate endpoints (levels of interleukins and C-reactive protein (CRP)) or LOSH. A reduction in mortality has not been shown. Several recently published reviews and meta-analyses conclude that there is a benefit from perioperative and postoperative IN in patients undergoing major gastrointestinal surgery, but results remain inconsistent. Beneficial outcomes have been shown in a systematic review of 35 trials in patients undergoing elective surgery, in which arginine-supplemented diets were associated with a significantly reduced prevalence of infectious complications and LOSH. There is also evidence to suggest that immunemodulating nutrition may be more beneficial in undernourished rather than in normally nourished patients. However, IN could bedetrimental in patients with sepsis.46 There are no trials investigating IN within ERAS care pathways. Summary and recommendation: The balance of evidence suggests that IN for 5e7 days perioperatively should be considered because it may reduce the prevalence of infectious complications in patients undergoing major open abdominal surgery. K. Lassen et al. Clin Nutr 2012, 31: 817- 830

Preoperative ERAS components Patient information Health/medical optimisation Nutrition Fasting time Carbohidrate drinking Pre-anesthestic medication Anti-thrombotic prophylaxis U.O. Gustafsson et al. Clin Nutr 2012; 31: 783-800

Preoperative fasting “While it is desirable that there should be no solid matter in the stomach when chloroform is administered, it will be found very salutary to give a cup of tea about 2 h previously.” Joseph Lister . On anaesthetics, Holmes' system of surgery. Vol 3, 3rd ed. London: Longmans Green and Company, 1883

Ljungqvist & Söreide, Br J Surg, 2003; 90: 400-406 Preoperative fasting Standard practice – fasting from midnight reduce the volume and acidity of stomach contents decrease the risk of pulmonary aspiration But … Ljungqvist & Söreide, Br J Surg, 2003; 90: 400-406

Preoperative fasting Standard practice – fasting from midnight But … reduce the volume and acidity of stomach contents decrease the risk of pulmonary aspiration But … Cochrane review of 22 RCTs fasting from midnight no reduction in gastric content no rise in pH of gastric fluid clear fluids until 2h before anesthesia Thirst, headaches, hunger The most common surgical practice of making patients NPO (nil per os) after midnight of the day of any planned surgical procedure has been recently questioned. However; Brady et al. reviewed 38 randomized controlled trials on perioperative fasting and concluded that there was no evidence to suggest overnight fasting for fluids results in a decrease in perioperative aspiration risk or related morbidities Brady M, et al. Cochrane Database Syst Rev 2003;(4). CD004423.

Why challange fasting by midnight? Normal physiology Is no guarantee of an empty stomach The same gastric volume with/without clear fluids Improved well being Thirst, headaches, hunger

Preoperative fasting Standard practice Fasting from midnight Reduce the volume and acidity of stomach contents Decrease the risk of pulmonary aspiration Modern fasting guidelines Clear fluids 2 h before anaesthesia Exclusions Emergency surgery

Eur J Anaesthesiology 2011;28:556-569

What are the effects of the preoperative fasting ?

Preoperative fasting and perioperative fluids If fasted – risk of dehydration Dehydration and anesthesia -> hypotension Hypotension -> more fluids infused Overload of fluids Preop clear fluids -> less iv fluids -> improved outcomes Gustafsson et al Arch Surg, 2011

Metabolic effects of overnight fasting Day Night Hormones Insulin + Insulin – Glucagon Cortizol Substrates Storage Breakdown Utilization CHO > Fat Fat > CHO Ljungqvist O.et al. Scand J Nutr 2004; 48 (2): 77-82

Surgical stress Insulin resistance

Insulin sensitivity falls with the magnitude of surgery More Insulin Resistance Percentage (%) Thorell A et al, Curr Opin Clin Nutr Metab Care 1999; 2: 69

Insulin resistance cause complications Elective cardiac surgery, n= 273 Diabetics and non diabetics Complications increase with insulin resistance: 50% reduction in insulin sensitivity: 5-6 fold increase risk of complications 10 fold risk for infections Sato et al, JCEM 2010, 95; 4338-44

Can we change the metabolism ?

Preoperative ERAS components Patient information Health/medical optimisation Nutrition Fasting time Carbohidrate drinking Pre-anesthestic medication Anti-thrombotic prophylaxis U.O. Gustafsson et al. Clin Nutr 2012; 31: 783-800

Carbohydrate treatment 20% glucose iv 12.5% carbohydrate drink – 400 ml 2h before anesthesia + 800 ml evening before Induce insulin release Aims: Insulin response Insulin resistance is one of the most fundamental reactions to injury and stress (1). In response to an injury, the activation of the neuroendocrine and inflammatory systems very rapidly (within minutes) sets the body in a metabolic state of stress. This includes a halt of anabolic processes, and instead substrates from all bodily stores (fat, carbohydrate, and protein) are released and made available as fuels, as building blocks for acute phase proteins or tissue healing. Central to this potentially massive change in metabolism is the development of insulin resistance. Insulin is the body’s most important anabolic hormone, and to achieve the rapid mobilization of substrates, insulin actions are reduced. In surgical patients, the degree of insulin resistance is related to the magnitude of the operation (1). In major surgical procedures, such as major colorectal operations, up to 90% of the preoperative insulin sensitivity can be lost after the operation. This change in metabolism lasts for well over 1 wk, even after moderate surgical stress. What is now becoming more and more evident is that insulin resistance is one of the key mechanisms by which several common surgical complications are triggered. Traditionally, insulin resistance was regarded as the way the body should respond to stress, and for the most part it was believed that it was probably beneficial and purposeful and should not be interfered with. Indeed, in studies of certain situations of severe stress, insulin resistance can be a key for survival. This is true in acute hemorrhage, where insulin resistance is needed to mobilize glucose to achieve fluid movements and plasma refill (2). However, in contrast to this, recent studies in elective surgical patients have suggested that in modern surgical practice, insulin resistance is harmful by prolonging recovery (1), and in this issue of JCEM Sato et al. (3) present a very important study showing a clear relationship between insulin resistance and postoperative complications.

What is the effect of the carbohydrate drink ?

Setting before surgery Fasted CHO fed Hyperglycemia - + Insulin sensitivity + 50% Glucose production - - - Peripheral glucose uptake + + + Ljungqvist et al, Clin Nutr 2001 , Svanfeldt et al Clin Nutr 2005

Carbohydrate treatment 20% glucose iv 12.5% carbohydrate drink – 400 ml 2h before anesthesia + 800 ml evening before Safety ???

Carbohydrate treatment Gastric emptying is complete in 90 min for CHO / water 120 90 60 30 20 40 80 100 * CHO, n=6 Water, n=6 Isotope activity in the stomach (%) Minutes after intake Nygren et al, Ann Surg, 1995

Oral intake of CHO does not increase gastric volumes Gastric volume (ml) Acidity (pH) Overnight fast (n=89) 6-41 1.6-4.0 Placebo (n=86) 12-35 1.6-2.5 CHO 12.5 % (n=80) 7-41 1.6-2.7 400 ml 12.5% carbohydrate rich drink, 360 mosm/kg Hausel et al, Anesth Analg 2001

Carbohydrate treatment 20% glucose iv 12.5% carbohydrate drink – 400 ml 2h before anesthesia + 800 ml evening before Safe – fast gastric emptying

Preop CHO reduces postoperative insulin resistance Control Per cent change from preop * * * * More resistance Nygren et al: Curr Opin Clin Nutr Metab Care 2001

Preop CHO activates muscle insulin signalling pathways Wang et al, BJS 2010

Preop CHO maintains postoperative muscle anabolic pathways Wang et al, BJS 2010

Preoperative CHO retains lean body mass (MAC) [cm] P <0.05 Yuill et al, Clin Nutr 2005 66

Effects of preoperative carbohydrates Reduces the metabolic stress of surgery Effectively reduces insulin resistance Improves pre/postoperative well being Improves postoperative muscle function Reduce lean body mass losses May result in faster recovery

What type of carbohydrates ?   Clear carbohydrate drink ONS 400  (70g ONS dissolved in water to 400 ml) ONS 300 (70g ONS dissolved in water to 300 ml) Amount ingested 400 ml 300 ml Amount of carbohydrate 50g Amount of protein 0g 15g glutamine

What type of carbohydrates ?

Preoperative carbohydrates Eur J Anaesthesiology. 2011;28:556-569

Preoperative carbohydrates Meta analysis Length of Stay The traditional practice of overnight fasting has definitively been shown to be unnecessary and numerous anaesthesia societies have now changed their guidelines to permit more liberal fluid intakes47 up to 2 h prior to induction of anaesthesia. Findings from the present meta-analysis indicated preoperative carbohydrate treatment was not associated with an increase in drink-related complications; confirming the safety of utilising oral complex carbohydrate drinks of appropriate osmolality preoperatively. Several countries have already updated their preoperative guidelines to recommended preoperative carbohydrate treatment due to its perceived beneficial effects on insulin resistance and wellbeing. 48 This meta-analysis also suggests that, in addition to the aforementioned benefits, faster recovery (decreased length of hospital stay) in patients undergoing open major abdominal surgery may also be expected. Preoperative carbohydrate treatment, as part of a multimodal enhanced recovery protocol, is recommended by the Enhanced Recovery After Surgery (ERAS) One day shorter length of stay for major abdominal surgery, n = 762 No difference in minor short stay surgeries (<3 days), n =380 No difference in orthopedic surgery, n = 32 Awad et al, ClinNutr 2013; 32 : 34-44

All recent Guidelines recommend oral carbohydrate loading Germany 2003: Major surgery Anaesthesist. 2003 Nov;52(11):1039-45. Scandinavia 2005: Major surgery Acta Anaesthesiol Scand. 2005 Sep;49(8):1041-7 ESPEN 2005: Major surgery Clin Nutr. 2006 Apr;25(2):224-44 ESPEN 2009: Major surgery Clin Nutr. 2009 May 20 United Kingdom 2009: Elective surgery J Intensive Care Society. 2009;10(1):13-5 European Soc Anesthesiology 2011: Elective surgery Eur J Anaesthesiology. 2011;28:556-569

Preoperative ERAS components Patient information Health/medical optimisation Nutrition Fasting time Carbohidrate drinking Pre-anesthestic medication Anti-thrombotic prophylaxis U.O. Gustafsson et al. Clin Nutr 2012; 31: 783-800

Pre-anesthetic medication Education Avoid starvation CHO loading No sedative medication before surgery Short-acting iv drugs Prior epidural/spinal analgesia U.O. Gustafsson et al. Clin Nutr 2012; 31: 783-800

Preoperative ERAS components Patient information Health/medical optimisation Nutrition Fasting time Carbohidrate drinking Pre-anesthestic medication Anti-thrombotic prophylaxis U.O. Gustafsson et al. Clin Nutr 2012; 31: 783-800

Anti – thrombotic prophylaxis Risk in colorectal surgical patients DVT – 30% PE – 1% Mechanical Pharmacological Compression stockings in all patients Intermitent pneumatic compression LMWH for 28 days in cancer patients U.O. Gustafsson et al. Clin Nutr 2012; 31: 783-800

Intraoperative ERAS components Antimicrobial prophylaxis Anesthesia protocol PONV Fluid management Hypotermia prophylaxis

Intraoperative ERAS components Antimicrobial prophylaxis Anesthesia protocol Multimodal analgesia PONV Fluid management Hypotermia prophylaxis

Antimicrobial prophylaxis Imperative to reduce the risk of surgical infections Time 30-60 min before the incision repeated doses during prolonged procedure (≥3h) Massive blood loss/fluid loading Route intravenous Spectrum Suspected germs (aerobic ± anaerobic bacteria)

Intraoperative ERAS components Antimicrobial prophylaxis Anesthesia protocol PONV Fluid management Hypotermia prophylaxis

Anesthetic protocol Target – rapid awake of the patient Anesthesia technique Balanced anesthesia TIVA Short acting agents Hypnosis – propofol, sevoflurane, desflurane Analgesia – sufentanil, remifentanil Myorelaxant – cisatracurium Algésimètre pupillaire pour le monitorage de l'analgésie

Intraoperative Monitoring BIS Hypnosis Muscle relaxation Cardiac output Glucose Analgesia Algiscan TOF ERAS Oesophageal doppler Glucometer

Intraoperative ERAS components Antimicrobial prophylaxis Anesthesia protocol Multimodal analgesia PONV Fluid management Hypotermia prophylaxis

Multimodal analgesia Epidural analgesia iv analgesia Wound catheters/infiltration Peripheral blocks

Benefits of Epidural Analgesia Dynamic pain control Obtunds stress response Reduction of ileus Reduced post-operative pulmonary complications Reduced myocardial ischaemia Reduced incidence of DVT/PE

Causes of ileus Degree of surgical manipulation Magnitude of inflammatory and stress response Sympathetic reflexes Opioids Fluid overload/ bowel oedema

Epidural analgesia vs iv opiates GI function EDA results in less GI paralysis Jorgensen Cochr Database Syst Rev 2004

Intraoperative ERAS components Antimicrobial prophylaxis Anesthesia protocol Multimodal analgesia PONV Fluid management Hypotermia prophylaxis

PONV Risk factors Patient: female, non smokers, motion sickness Anestetic: volatile agents, iv opioids, nitrous oxide Surgical: major abdominal surgery PONV scoring systems Multimodal approach Pharmachological Non-pharmachological techniques: TIVA, minimal fasting, CHO loading, adequate hydration, epidural, NSAIDS

Intraoperative ERAS components Antimicrobial prophylaxis Anesthesia protocol Multimodal analgesia PONV Fluid management Hypotermia prophylaxis

Perioperative fluid management Is fluid therapy vital for outcome ? Are the fluid requirements the same ? What about fluid shifts ? What amount ? What type of fluid ? Is there an indication for vasopressors ? When iv fluids should be discontinued ? Is fluid therapy vital for an optimal outcome after surgery ?

Post-op Weight Gain Following Colorectal Resection KCH Fearon 2004 Post-op Weight Gain Following Colorectal Resection 3-6kg Lobo et al, Lancet Brandstrup et al, 2002; 359: 1812-18 Annals Surg 2003; 238: 641-8

Perioperative fluid management DO2 = CO (SV x HR) x CaO2 x 10 Bundgaard-Nielsen,et al. Acta Anaesth Scand 2009, 53: 843–851

Preoperative carbohydrates, fluids and outcomes Main factors for better outcomes: Preop carbohydrates & fluid balance Preop carbohydrates -> Less fluid overload (450 ml) For every litre extra*: 32% increased risk of complications (cardiovascular) * Limit: Day of surgery: Colonic 3,000 ml, Rectal 3,500 ml Gustafsson et al, Arch Surg 2011

Fluid requirements are different Open laparatomy Increase fluid shifts Bowel handling SIRS Laparoscopy CO reduction Head-down position Pneumoperitoneum

Fluid shifts should be minimised Avoid bowel preparation Maintain hydration till 2 hours before surgery Minimise bowel handling Avoid blood loss exteriorisation outside the abdominal cavity

The use of cardiac output / surrogate Goal Directed Therapy The use of cardiac output / surrogate to guide iv fluid alone or in combination with inotropics during the perioperative period.

Goal directed intra-operative fluid therapy Noblett et al. BJS 2009

Meta analysis based on amount of fluid given <1.75 liters/24h >2.75 liters/24h Varadhan K, Proc Nutr Soc, 2010

Fluids – recent meta‐analysis Rahbari NN, BJS 2009: 96: 331

Types of fluids cristaloids and coloids Body water compartments

59% reduced risk for complications Varadhan K, Proc Nutr Soc, 2010 59% reduced risk for complications 3.4 days reduction in hospital stay

Perioperative fluid management Fluid therapy is vital for outcome Fluid requirements are different Fluid shifts should be minimised Fluid administration must be goal directed The types of fluids – cristaloids and coloids Vasopressors are indicated in hypotensive normovolemic patients Iv fluids should be discontinued as soon as practicable

Intraoperative ERAS components Antimicrobial prophylaxis Anesthesia protocol Multimodal analgesia PONV Fluid management Hypotermia prophylaxis

Hypothermia prophylaxis Hypothermia – central temperature < 36 C Risk factor for wound infections, prolonged cicatrisation cardiac events shivering – increase O2 consumption bleeding coagulation disorders trombocites dysfunction postoperative ileus increase pain prolonge emergence time

Hypothermia prophylaxis Hypothermia – central temperature < 36 C Methods warming devices (forced air warming blankets) warmed iv fluids warm gases in laparoscopic surgery

Postoperative ERAS components Postoperative analgesia Fluid management Postoperative glycaemic control Postoperative nutrition Early mobilisation

Postoperative analgesia Optimale analgesic regimen Good pain relief Reduction of cardiovascular, cognitive, endocrino – metabolic complications in at risk patients Decrease the risk of chronic pain Allow early mobilisation Allow early return of gut function and feeding

Postoperative analgesia Principles of Multimodal Analgesia Avoidance of iv opioids Regional anesthesia techniques Thoracic epidural analgesia (TEA) Spinal analgesia Local anesthetic techniques Transversus abdominis plane (TAP) block The analgesic regimen is specific to the type of surgery/incision

Postoperative analgesia in open surgery Thoracic epidural anesthesia (TEA) Middle thoracic (T7-T10) Superior analgesia in the first 72 h Earlier return of gut function

Postoperative analgesia in open surgery Thoracic epidural anesthesia (TEA) Low dose concentration of local anesthetic Short acting opiate Maintained for 48 -72 h postoperative

Efficacy of Postoperative Epidural Analgesia: A Meta-analysis Block BM et al, JAMA. 2003;290(18):2455-2463

Epidural analgesia vs opiates GI function EDA results in less GI paralysis (vs iv opiates) Jorgensen Cochr Database Syst Rev 2004

Postoperative analgesia in laparoscopic surgery Spinal analgesia Low dose long acting opioid- morphine Recent publications have shown that the duration of pain after laparoscopic surgery requiring major analgesics is much shorter than for open surgery, thereby allowing discharge from hospital as soon as 23 h after surgery. Provided early feeding is tolerated in the laparoscopic group, analgesic requirements at 24 h postoperatively are often addressed with oral multimodal analgesia without the need of regional blocks or strong opiates

Modification of ERAS in lap surgery ? RCT EDA vs Spinal vs PCA, n=91 Lap colorectal surgery LOS EDA (3.7 d) longer than PCA and Spinal (2,8 and 2,7 d) Spinal Faster return of bowel function (vs EDA and PCA) Earlier tolerance of food (vs EDA) Levy, BJS, 2011

ERAS and Lap colorectal resection One center (North Bristol, UK), n=606, 2004-2009 Primary anastomosis ERAS formally after 2008 Transversus abdominis plane (TAP) or rectus sheath block No EDA or PCA KAD withdrawn in theatre 46% discharged within 3 days (Median LOS 4 days) 2 same day, 70 within 24 hrs, 116 within 48 hrs, 91 within 72 hrs Readmission rates 4 %, Gash KJ, Colorectal Dis, 2012

Early removal of KAD during EDA ? During thoracic epidural anesthesia Removal of KAD in the morning after surgery Or after removal of EDA RCT, N=205 No increased need for recatheterization Transient increase in post-void residual volume (UL Scanning) Zaouter, Acta Anasth Scand, 2012

Postoperative ERAS components Postoperative analgesia Fluid management Postoperative glycaemic control Postoperative nutrition Early mobilisation

59% reduced risk for complications Varadhan K, Proc Nutr Soc, 2010 59% reduced risk for complications 3.4 days reduction in hospital stay

Postoperative ERAS components Postoperative analgesia Fluid management Postoperative glycaemic control Postoperative nutrition Early mobilisation

Postoperative glycaemic control

Hyperglycemia in surgical stress Insulin resistance is the key Traditional belief Hyperglycemia in the acutely stressed patient is ”not dangerous” Glucose levels treated > 200 mg/dl

hyperglycaemia can be avoided Elective major surgery opportunity to prevent /attenuate metabolic responses to surgery rather than having to treat them with insulin. Several stress-reducing interventions in ERAS attenuate insulin resistance as single interventions: preoperative oral carbohydrate treatment epidural blockade minimally invasive surgery If interventions are combined in ERAS protocol, hyperglycaemia can be avoided even during full enteral feeding starting immediately after major colorectal surgery.

Postoperative ERAS components Postoperative analgesia Fluid management Postoperative glycaemic control Postoperative nutrition Early mobilisation

Postoperative nutrition Fluids immediately after recovery from anesthesia Normal hospital food on day 1  traditional care  enhanced-recovery protocol Nygren Clin Nutr 2003

Postoperative early enteral nutrition No increased risk of anatomotic leaks, reduce risk of infection and LOS Without multimodal anitiileus therapy – increased risk of vomiting Watters: upper major GI-surgery, jejunostomy Lewis et al BMJ 2001;323(7316):773-6

Postoperative ERAS components Postoperative analgesia Fluid management Postoperative glycaemic control Postoperative nutrition Early mobilisation

Early mobilisation EFFECTS CONDITIONS Early return of bowel function Improved digestive tolerance Enhanced anabolism Decreased risk of venousthromboembolism Deacreased risk of pulmonary complications Enhanced recovery !!! CONDITIONS Good analgesia No ventilatory support No postoperative somnolence Psycological support

Outline Anesthetist approach Surgeon approach Protocolization

”It is ironic that the American Society of Anesthesiologists, whose members are critical observers of surgical procedures, evolved the best index of “operative risk”. Arthur S. Keats, Anesthesiology 1978

” Perhaps the American Surgical Association, whose members are critical observers of anesthetic procedures, will provide us with a meaningful index of “anesthetic risk”. Arthur S. Keats, Anesthesiology 1978

Surgeon: Anesthetist: No bowel prep Food after surgery No drains or KAD No iv fluids, no lines Early discharge All evidence based! Anesthetist: Carbohydrates No fasting No premedication Epidural Anesthesia Balanced fluids Vasopressors No or short acting opioids

EVIDENCE BASED MEDICINE SURGEONS!! TRADITION EVIDENCE BASED MEDICINE

BOWEL PREPARATION PRO CON Avoids massive contamination !?! Minor inconvenience to the patient !?! Looks better inside !?! CON Preoperative dehydration !!! Modification of enteral flora !!! Delayed gut motility !!!

CONCLUSIONS: 7 trialuri 1300 pt Arch Surg. 2004 Dec;139(12):1359-64; discussion 1365. Mechanical bowel preparation for elective colorectal surgery: a meta-analysis. Bucher P, Mermillod B, Gervaz P, Morel P. CONCLUSIONS: 7 trialuri 1300 pt There is no evidence to support the use of MBP in patients undergoing elective colorectal surgery. Available data tend to suggest that MBP could be harmful with respect to the incidence of anastomotic leak and does not reduce the incidence of septic complications.

Rectal cancer – TME (total mesorectum excision) Standardised Enhanced Recovery Programme for the EnROL Trial Day before surgery avoidance of oral bowel preparation except in patients undergoing total mesorectal excision (TME) and reconstruction. Kennedy et al. BMC Cancer 2012, 12:181

Reduce surgical injury Minimally invasive surgery FAST TRACK Surgery Early postoperative recovery Decreased stress response Decreased inflammatory response Decreased pain Early bowel movement

shortens hospitalization FAST TRACK Early rehabilitation Minimally invasive surgery NOT MANDATORY for FAST TRACK surgery but shortens hospitalization

NO routine nasogastric tube 28 multicenter trials >4000 pts Decreased duration of postoperative ileus Decreased risk of postoperative pulmonary complications Increased patient QOL No increase in anastomotic leak Nelson, R. at all Systematic review of prophylactic nasogastric decompression after abdominal operations. Br. J. Surg., 2005, 92, 673–680.

No drains Rationale of drains: “When in doubt, drain” A surgical tradition Difficult to be abandoned For how long? 24h / 48h / 7days ??? In majority of cases – serous drained fluid (physiological reabsorption) “When in doubt, drain” Lawson Tait, english surgeon “The drain= the surgeon eye in the patients abdomen”

No drains RCTs: Unreliable indication of anastomotic leak Underestimates the significance of anastomotic leak Underestimates the postoperative bleeding Does not influence the rate of anastomotic leak Increases the contamination risk Prolongs the duration of postoperative ileus Prolongs the hospital lenght of stay Petrowsky, H. at all: Evidence-based value of prophylactic drainage in gastrointestinal surgery: A systematic review and meta-analyses. Ann. Surg., 2004, 240, 1074–1085.

Day of surgery – postoperative period IV fluids, if clinically indicated pressors for epidural hypotension regular pre-emptive antiemetics (ondansetron as first line) Early mobilization (patient sits up) Starts drinking protein drinks COLONIC SURGERY

Day 1 Day 2 Urinnary catheter removed in the morning 8 hrs of enforced mobilisation Resumes normal diet Pre-emptive oral analgesia is started Paracetamol and NSAIDs Avoid Opioids Day 2 Epidural infusion is stopped in the morning Epidural Catheter is removed at 14.00 if pain controlled and timed with anticoagulant dose COLONIC SURGERY

is an important target for patients and staff but flexibility is vital Day 3/4 - discharge criteria: Return of GI function Able to eat and drink without discomfort Passing flatus Pain controlled with oral analgesia Adequate home support Discharge date is an important target for patients and staff but flexibility is vital COLONIC SURGERY

THE SURGEON the cornerstone of FAST TRACK and ERAS programs

Outline Anesthetist approach Surgeon approach Protocolization

Preoperative optimisation Preoperative nutrition Preoperative Fasting Carbohydrates Treatment Properative prophylaxys Preventing hypotermia Analgesia Fluid management PONV Fluid management Postoperative nutrition Early mobilisation Analgesia

1. ERAS Results? Randomised trials Meta analysis

ERAS compliance & outcomes 953 consecutive colorectal surgery patients Multi variate analysis – ERAS factors Carbohydrate treatment 44% reduced risk of symptoms delaying discharge (PONV, pain, GI sympoms, dizziness ) 16% reduced risk of wound dehiscence Fluid balance: For each extra Liter 16% increased risk of symptoms delaying discharge 32% increased risk of complications Gustafsson et al Arch Surg, in press 2011

ERAS - clinical outcome Review of 6 RCTs (n=452) Complications Reduce complications by 50% Review of 6 RCTs (n=452) The results from the present meta-analysis suggest that the implementation of four or more elements of the ERAS pathway leads to a reduction in length of hospital stay by more than 2 days. However, there was significant heterogeneity for the effect of ERAS on the length of hospital stay and hence, could potentially weaken the treatment effect. K K. Varadhan et al. Clin Nutr, 2010: 29 ;434–440

ERAS - clinical outcome Review of 6 RCTs (n=452) Mortality Of the 452 patients, 4 died during the 30 day follow-up period, with one death (myocardial infarction) in the ERAS group and three ( 2 myocardial infarctions and 1 pulmonary embolism) in the traditional care group. K K. Varadhan et al. Clin Nutr, 2010: 29 ;434–440

ERAS - clinical outcome Review of 6 RCTs (n=452) Length of stay Shorter length of stay by 2.5 days Review of 6 RCTs (n=452) The results from the present meta-analysis suggest that the implementation of four or more elements of the ERAS pathway leads to a reduction in length of hospital stay by more than 2 days. However, there was significant heterogeneity for the effect of ERAS on the length of hospital stay and hence, could potentially weaken the treatment effect. K K. Varadhan et al. Clin Nutr, 2010 : 29 ;434–440

Experimental group= Enhanced Recovery After Surgery (ERAS) Readmissions (days) no significant difference was noted in readmission rates Experimental group= Enhanced Recovery After Surgery (ERAS) Control = Traditional Care (TC)

JAMA Surgery 2011

International Journal of Colorectal Disease “Fast-track” rehabilitation after colonic surgery in elderly patients—is it feasible? International Journal of Colorectal Disease Volume 22, Number 12 / December, 2007 M. Scharfenberg1, W. Raue1, T. Junghans1 and W. Schwenk1  Conclusion  Using the “fast-track” rehabilitation programme on elderly patient is not only feasible but may also lower the number of general complications and the duration of the hospital stay. Ciaran O’Hare Ciaran O’Hare

Fast-Track Concepts in Major Open Upper Abdominal World J Surg. 2011 Sep 1. Fast-Track Concepts in Major Open Upper Abdominal and Thoracoabdominal Surgery: A Review. Fagevik Olsén M, Wennberg E. 15 articles: gastric (n = 2), pancreatic (n = 5), hepatic (n = 2), esophageal (n = 3), aortic surgery (n = 3) .

Sipos P, HMJ, 2007 Vol.1, Number 2,165–174

successful fast-track surgery program. Anesth Analg 2007;104:1380-1396 © 2007 International Anesthesia Research Society doi: 10.1213/01.ane.0000263034.96885.e1 AMBULATORY ANESTHESIA The Role of the Anesthesiologist in Fast-Track Surgery: From Multimodal Analgesia to Perioperative Medical Care Paul F. White, PhD, MD*, Henrik Kehlet, MD, PhD , and the Fast-Track Surgery Study Group CONCLUSION: The decisions of the anesthesiologist as a key perioperative physician are of critical importance to the surgical care team in developing a successful fast-track surgery program.

ORIGINAL ARTICLE Current perioperative practice in rectal surgery in Austria and Germany Till Hasenberg, Friedrich Längle, Bianca Reibenwein, Karin Schindler,  Stefan Post, Claudia Spies,Wolfgang Schwenk and Edward Shang INTERNATIONAL JOURNAL OF COLORECTAL DISEASE 2010 Volume 25, Number 7, 855-863, DOI: 10.1007/s00384-010-0900-2 Results The response rate - 63% A (76 centers) + 30% G (385 centers). Mechanical bowel preparation - abandoned by 2% G and 7% A surgeons. Nasogastric decompression tubes - rarely used; 4/5 of the questioned surgeons - use intra-abdominal drains. Half of the surgical centers - intake of clear fluids on the day of surgery. Mobilization - in half of the centers on the day of surgery. Epidural analgesia - three-fourths of the institutions. Institutions which have implemented fast track rehabilitation discharge earlier.

“Surgery and peri-operative care remains heavily based in tradition” Practice varies substantially internationally survey of UK general surgeons: ‘there is inadequate multidisciplinary and community support’ to initiate ERAS ‘never heard of it’. survey regarding practice across European countries: ‘nil by mouth’ almost abandoned in others This is the biggest challenge facing the wide implementation and acceptance of ERAS programs. Hill, Andrew (2008, December 10). Enhanced Recovery after Surgery. SciTopics. http://www.scitopics.com/Enhanced_Recovery_after_Surgery.html

multi-modal care programmes Current evidence supports the potential role of multi-modal care programmes in the promotion of early recovery from major surgical trauma.  To achieve the desired outcome targets, all elements of the protocol must function, a committed, multidisciplinary approach is essential and a simple, but effective implementation and reinforcement strategies are necessary. Implementation in Practice (C.H.C. Dejong, Netherlands) http://www.jspen.jp/doc6/sec7.html

Implementation of the ERAS protocol select a target invite participation to create a team explain what you are trying to achieve select an “expert group” create change concept and priorities implement strategy regular review to measure and evaluate change review strategy Implementation in Practice (C.H.C. Dejong, Netherlands) http://www.jspen.jp/doc6/sec7.html

“There is nothing new under the sun but there are lots of old things we don’t know.” Ambrose Bierce.