ERYTHROMYCIN V' METOCLOPRAMIDE

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ERYTHROMYCIN V. METOCLOPRAMIDE

• For Gastric Emptying in the Full Stomach Patient
  Population

Nicole Sadowski Nurse Anesthesia Candidate Class
of 2010 Duke University School of
Nursing February 23, 2009
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EVERYDAY WE DEAL WITH FULL STOMACH
PATIENTSWHAT ARE FULL STOMACHS ANYWAYS???
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FULL STOMACHS ARE
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FULL STOMACHS ARE
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FULL STOMACHS ARE.
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SO WHATS THE BIG DEAL????

• Aspiration riskespecially if gastric volume is
  gt25 mls with a pH lt2.5
• Aspiration pneumonitis
• Increased length of hospital stay
• Poor outcomes
• Increased cost
• Death
• Bad for us as providers if our patients aspirate,
  so what can we do to prevent it.

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LETS REVIEW SO WE KNOW WHAT WERE TALKING ABOUT,
SO WE KNOW WHAT WERE DEALING WITH!!

• Lets gab about the gut
• Review gastric hormones and motility
• Look at what we give as providers for aspiration
  prophylaxis
• What the literature has to say, well
  specifically look at erythromycin as a gastric
  prokinetic
• What changes we could make if any to current
  practices
• How could we make changes
• Questions/funny cartoons

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A REVIEW
LES constricted with intraluminal pressure of 30
mmHg
Body
Rugae
Duodenum
Pyloris
Antrum
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WHATS IN THERE ANYWAYS???

• Gastrinsecreted by G cells of antrum of the
  stomach and stimulates gastric acid secretion and
  GI motility
• Motilinsecreted by upper duodenum and stimulates
  upper GI tract motility
• Acetylcholineexcites gastrointestinal activity
• Serotoninenhances intestinal motility
• Insulin/glucagonexcitatory/inhibitory
• Epi/NEinhibit gastrointestinal activity
• Secretinsecreted by S cells in mucosa of
  duodenum in response to acidic gastric juices
  has an inhibitory effect on motility of small
  intestine

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THESE HORMONES ARE SECRETED IN RESPONSE TO.
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THE STOMACH IS A REAL ACID TRIP!!
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PARIETAL CELLS

• Secrete hydrochloric acid
• pH of 0.8
• 3 million x that of arterial blood
• To concentrate H ions, more than 1500 calories
  of energy per liter of gastric juices are
  required
• And we make 6700 mls of intestinal juices
  dailyincluding bile, small/large intestine,
  gastric, secretions, and saliva
• Which may help you see

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WHERE
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ALL
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THIS
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DROOL
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COMES
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FROM
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BUT SOMETIMES, DROOL ISNT ALL BAD
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ENTEROCHROMAFFIN-LIKE CELLS

• Work in close association with parietal cells
• Release histamine
• Rate of formation/secretion of HCL by parietal
  cells is directly related to the amount of
  histamine secreted by ECL cells
• Can be stimulated by gastrin and acetylcholine
• What does this mean for us as anesthesia
  providers???

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WE START THINKING ABOUT PROPHYLAXIS FOR OUR
PATIENTS
Reglan
Reglan
Esomeprazole
Ranitidine
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WHICH IS INDICATED FOR MANY PTS

• Full stomachs, who are at greater risk for
  aspiration of gastric contents
• Obeselarger volumes and more acidic gastric
  contents than their normal-weight counterparts
• Diabeticsimpaired gastric emptying because of
  this metabolic disorderd/t roles of insulin,
  glucagon, and blood sugar levels
• Bowel obstruction
• GERD
• Pregnant
• Trauma
• Gastroparesis
• PUD
• And.

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THE GUY WHO JUST ATE THIS ON THE WAY TO SURGERY
THIS AFTERNOON
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SO WHAT DO WE DO FOR THESE PTS?

• RSI with cricoid pressure, which is the intended
  occlusion of the esophagus by means of pressure
  applied to the cricoid cartilage at the level of
  cervical vertebrae 6
• Proton Pump Inhibitorsprazoles, like omeprazole
• H2 Receptor Blockerstidines, like ranitidine
• Non-particulate antacids, like bi-citra
• Antiemetics before, during, or the end of
  surgery, such as Zofran, Decadron, droperidol or
  scopolamine patch
• Maybe not using N20another day

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AND.

• Dopamine receptor antagonists, such as
  metoclopramide
• Increases motility and accelerates gastric
  emptying
• Sensitizes the gastrointestinal tracts response
  to acetylcholine and increases lower esophageal
  sphincter tone
• Widely used as a prokinetic agent prior to
  anesthesia.
• Side effects include abdominal cramping,
  restlessness, sedation, and extrapyramidal side
  effects such as dystonia and tardive dysknesia

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BUT WHAT ABOUT ALTERNATIVES?

• Erythromycin, a broad-spectrum macrolide
  antibiotic
• An effective gastric prokinetic at sub-antibiotic
  doses
• typically 200-250 mg or 2-3 mg/kg (Bala, Prasad,
  Bhukal, Dhiraj, and Pratap, 2008)
• A motilin receptor agonist, and possibly causes
  endogenous motilin release to promote gastric
  contractions (Bouvet, Duflo, Bleyzac, Mion,
  Boselli, Allaouchiche et al., 2006)
• Increases lower esophageal sphincter pressure,
  and enhances antroduodenal (stomach and small
  intestine) coordination (Kopp, Mayer and Shaheen,
  1997)
• Promotes solids/liquids emptying, reduces
  gastric volume and acidity, is effective
  intravenously or orally in healthy and
  gastroparetic pts (Asai, Murao and Shingu, 2000).
  

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• Potent gastric prokinetic effects
• Clinically significantcould reduce the risk of
  pulmonary aspiration in high-risk patient
  populations

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• Erythromycinfrequent use in gastroenterology
• Prior to endoscopy, used to empty blood from GI
  tract d/t bleeds, bleeding varicies, other
  gastrointestinal-related medical conditions
  (Kopp, Mayer and Shaheen, 1997)
• Currently, erythromycin is NOT used pre-op for
  gastric emptying and prevention of pulmonary
  aspiration

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WELL WHATS THE CATCH?

• Erythromycin is inexpensive
• Potent gastric prokinetic
• Doses used for prokinetic activity are small (2-3
  mg/kg, or about 200-250 mg)
• Sub-therapeutic antibiotic doses (therapeutic
  doses are 500-1000 mg)antibiotic resistance is
  of limited concern
• Side effectsGI-related nausea, vomiting,
  diarrhea, abdominal pain and gastrointestinal
  irritation
• Side effects are dose dependentunlikely at such
  small doses

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LETS DAY DREAM FOR A SECOND

• Congratulations to the class of 2009
• Good luck with studying
• With your boards
• Your futures
• Your careers!!

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A LOOK AT THE LITERATURE

• Study done in 2008 (Bala, et al.)investigated
  the effect of preoperative oral erythromycin,
  erythromycin-ranitidine, and ranitidine-metoclopra
  mide on gastric fluid pH and volume
• Ranitidine blocks histamine-2-receptors on the
  gastric parietal cells, preventing the secretion
  of gastric acid
• The patient population excluded all full
  stomach patients, were 8 hours NPO, and ASA I
  and II.

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BASICALLY YOUR DREAM PATIENTS
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FINDINGS SAY

• Divided into groups
• Administered combinations of placebo,
  erythromycin, ranitidine and metoclopramide
  before surgery
• After induction of anesthesia, gastric contents
  were aspirated via an OG tubegastric volume/pH
  were analyzed
• Erythromycin-ranitidine and ranitidine-metoclopram
  ide were equally effective in reducing gastric
  volume and acidity

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SO LETS EXPLORE FURTHER

• Asai, Murao, and Shingu (2000) found that
  pre-operative erythromycin reduced residual
  gastric volume and acidity
• Healthy patients, elective surgery, NO full
  stomachs
• Group 1NPO, half received erythromycin three
  hours before induction, half received water
• Significantly less residual gastric secretions,
  NO GI symptoms
• Good news!

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STILL EXPLORING

• Group 2half received erythromycin one hour
  before induction, half received water
• Gastric contentsaspirated via OG, volume/acidity
  studied
• Erythromycin reduced residual gastric volume in
  both groups (P lt 0.05 and P lt 0.0005
  respectively)
• Reduced gastric acidity given one hour before
  anesthesia (P lt 0.02)
• No adverse side effects experienced
• They postulated erythromycin reduces gastric
  acidity through a direct effect on motilin
  receptors

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WHY NOT OUR FULL STOMACHS???

• Thinking outside the box
• Erythromycin pre-op as aspiration prophylaxis
  for the full stomach patient population

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WHAT DID THEY FIND???

• Kopp, Mayer, and Shaheen (1997)
• Case study using IV erythromycin as prokinetic
• Emergency esophagogastroduodenoscopy (EGD) d/t
  bleeding esophageal variciesbanded, but re-bleed
  suspected fourth post-procedural day
• Pt ate before induction, received erythromycin
• Endoscopy confirmed gastric emptying
• Total lack of solids/liquids or clotted blood
• No other treatments given for gastric emptying,
  and spontaneous emptying unlikely
• First to askwhy not routinely use erythromycin
  for aspiration prophylaxis in high-risk patients?
  

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AND WHATS MORE

• Bouvet, Duflo, Bleyzac, Mion, Boselli,
  Allaouchiche et al. (2006)
• Two groups of ASA I and II patients
• Special meal plus Tylenol (measure gastric
  emptying by breath samples and Tylenol blood
  levels)
• Received erythromycin v. saline, then a painful
  stimulus (hand submerged in ice water) was
  applied
• Demonstrated acute stress prolongs gastric
  emptying of solid foods, but erythromycin
  attenuates this effect

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WHY IS THIS IMPORTANT???

• Surgical patients are under stress
• Even if healthy and not full stomachs, stress
  delays gastric emptying
• So now you DO have a full stomach/aspiration
  risk
• What about patients in pain/SNS activation?
• Narcotics/NSAIDS/adrenaline/hyperglycemiadecrease
  GI motility increase aspiration risk

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AND IF THATS NOT ENOUGH

• Several other studies results showed erythromycin
  is statistically, significantly effective in
  promoting gastric emptying in the presence of
  gastroparesis caused by diabetes, gastric reflux,
  trauma and critical illness (i.e., full
  stomachs)
• Berne, Norwood, Clyde, McAuley, Vallina,
  Villareal et al., (2002), Chrysos, Tzovaras,
  Epanomeritakis, Tsiaoussis, Vracasotakis,
  Vassilakis et al., (2001), and Boivin and Levy,
  (2001).

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MAYBE ITS TIME FOR CHANGE
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RECAP

• Not using erythromycin in the surgical setting
• Is used in gastroenterology
• Is effective in healthy patients as shown by
  clinical trials
• Is used in critically ill patient populations
  (promotes tolerance to tube feedings, for
  example)

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AH, THE ICU
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REMIND ME WHY NOT

• Not using erythromycin because of lack of large
  scale trials in surgical setting
• Not using it because certain populations havent
  been explored or have been explored minimally
• Such as the obeseno studies done to date
• Such as traumasin surgical setting
• Such as pregnantits always hard when unborn
  fetuses are involved
• Not using because it is not an antiemetic?
• Not using because we have always have not used it

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WHAT TO DO
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TELL ME, NIKKI, WHAT DO YOU THINK?

• We should explore erythromycin further
• Reglan has potential for serious side effects
• Erythromycin generally lacks side effects and
  antibiotic resistance at low doses
• Inexpensive
• More effective than Zantac or Reglan alone
  because it effects volume and acidity
• Proven effective in populations with aspiration
  risk that, if presenting for surgery, would be
  considered full stomachs, like GI bleeds, or
  pain pts with opioid-induced gastroparesis.
• More studies are needed on large scale

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A VERY LARGE SCALE!!
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TELL ME MORE

• Americans are frequently in need of prophylaxis
• 2/3 are in the overweight/obese categoriesGERD,
  hernias, and many other problems
• Co-morbidities associated with obesity alone can
  cause patients to be qualified as full
  stomachs, such as gastroparesis secondary to
  diabetes
• Traumas, pregnant, diabetics, bleeding ulcers
• Procedures can cause nausea/vomiting
• Idea of procedure can cause serious stress
• Both put the patient at risk for pulmonary
  aspiration of gastric contents

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WHAT NEEDS TO BE DONE

• Few studies performed in full stomach surgical
  patients
• Need large scale clinical trial in operative
  setting
• Obese would be ideal, easy to find at Duke on a
  daily basis, and no studies have been done
  previously
• Study would be minimally invasive, have minimal
  risk, not geared towards kids/fetuses, so
  potentially easier to pass through IRB

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AND AS FAR AS IRB GOES.

• Maybe Not So Tough For Dr. Vacchiano

• But The Rest Of Us Need Help!!

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AND IF WE MADE IT THROUGH..

• Three study groups of obese, ASA IIs
• Reglan, erythromycin, and placebo
• Random assignment
• Receive one of the three interventions prior to
  induction of anesthesia
• Aspirate gastric contents in various positions
  through OG tube
• Analyze volume and pH
• Analyze data for statistical significance

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• Feasible at Duke, and study results could lead to
  integration of erythromycin into practice as
  aspiration prophylaxis pre-operatively for full
  stomach surgical patient populations

At Duke
By Any Of Us
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THIRD TIMES A CHARM

• Currently dont use erythromycin, no reason
• Studies support it as potent gastric prokinetic
• Few side effects, inexpensive
• Few studies in surgical population
• Fewer studies in full stomach surg population
• Based on literature, it should be explored
  further
• Could be beneficial for full stomach surgical
  patients in reducing aspiration risks
• Need large scale clinical trial to work towards
  initiating evidence-based change in standards of
  care for the full stomach surgical patient

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THANK YOU FUTURE (AND PRESENT) CRNAS!
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REFERENCES
Asai, T., Murao, K., and Shingu, K. (2000).
Pre-operative oral erythromycin reduces residual
Gastric volume and acidity. British Journal of
Anaesthesia, 85(6), 861-864. Bala, I., Prasad,
K., Bhukal, I., Dhiraj, N., and Pratap, M.
(2008). Effect of preoperative oral Erythromycin,
erythromycin-ranitidine, and ranitidine-metoclopr
amide on gastric Fluid pH and volume. Journal of
Clinical Anesthesia, 20, 30-34. Berne, J.,
Norwood, S., McAuley, C., Vallina, V., Villareal,
D., Weston, J., and McClarty, J. (2002).
Erythromycin reduces delayed gastric emptying in
critically ill trauma patients A randomized,
controlled trial. The Journal of Trauma, 53,
422-425. Boivin, M., and Levy, H. (2001).
Gastric feeding with erythromycin is equivalent
to transpyloric feeding in the critically ill.
Critical Care Medicine, 29 (10),
1916-1919. Bouvet, L., Duflo, F., Bleyzac, N.,
Mion, F., Boselli, E., Allaouchiche, B., and
Chassard, D. (2006). Erythromycin promotes
gastric emptying during acute pain in
volunteers. Anesthesia and Analgesia, 102,
1803-8. Chrysos, E., Tzovaras, G.,
Epanomeritakis, E., Tsiaoussis, J., Vracasotakis,
N., Vassilakis, J., and Xynos, E. (2001).
Erythromycin enhances oesophageal motility in
patients with gastro-oesophageal reflux. ANZ
Journal of Surgery, 71, 98-102. Frossard, J.,
Spahr, L., Queneau, E., Giostra, E., Burckhardt,
B., Ory, G., De Saussure, P., Armenian, B., De
Peyer, R., and Hadengue, A. (2002). Erythromycin
intravenous bolus infusion in acute upper
gastrointestinal bleeding A randomized,
controlled, double-blind trial.
Gastroenterology, 123, 17-23.
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REFERENCES CONTINUED
Ghoos, Y., Maes, B., Geypens, B., Mys, G., Hiele,
M., Rutgeerts, P., and Vantrappen, G. (2003).
Measurement of gastric emptying rate of solids
by means of a carbon-labeled octanoic acid
breath test. Journal of Clinical
Gastroenterology, 36 (3), 284-285. Keady, S.
(2007). Update on drugs for gastro-oesophageal
reflux disease. Archives of Disease in
Childhood, 92, 114-118. Kopp, V., Mayer, D.,
and Shaheen, N. (1997). Intravenous erythromycin
promotes gastric emptying prior to emergency
anesthesia. Anesthesiology, 87 (3),
703-705. Maganti, K., Onyemere, K., and Jones,
M. (2003). Oral erythromycin and symptomatic
relief of gastroparesis A systematic review.
The American Journal of Gastroenterology,
98(2), 259-263. Nagelhout, J., and Zaglaniczny,
K. (2005). Handbook of nurse anesthesia (3rd
ed.). St. Louis Elsevier Inc. Narchi, P.,
Benhamou, D., Elhaddoury, M., Locatelli, C., and
Fernandez, H. (1993). Interactions of
pre-operative erythromycin administration with
general anesthesia. Canadian Journal of
Anesthesia, 40 (5), 444-447. Petrakis, J.,
Kogerakis, N., Prokopakis, G., Zacharioudakis,
G., Antonakakis, S., Vrachassotakis, N., and
Chalkiadakis., G. (2002). Hyperglycemia
attenuates erythromycin-induced acceleration of
liquid-phase gastric emptying of hypertonic
liquids in healthy subjects. Digestive Diseases
and Sciences, 47 (1), 67-72.
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QUESTIONS????
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THE HISTORY OF ANESTHESIA2000 B.C. - "HERE,
TAKE THIS HAMMER."1000 B.C. - "THAT HAMMER IS
HEATHEN, SAY THIS PRAYER."1850 A.D. - "THAT
PRAYER IS SUPERSTITION, DRINK THIS POTION."1940
A.D. - "THAT POTION IS SNAKE OIL, SWALLOW THIS
PILL."1985 A.D. - "THAT PILL IS INEFFECTIVE,
TAKE THIS INHALATION"2000 A.D. - "THAT
INHALATION IS ARTIFICIAL. SHOW ME YOUR
BACK".2025 A.D. - "HERE, TAKE THIS HAMMER".