Journal Club Department of Anesthesia University of Ottawa

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Journal ClubDepartment of AnesthesiaUniversity
of Ottawa

• Successful use of a 20 lipid emulsion to
  resuscitate a patient after presumed
  bupivacaine-related cardiac arrest Rosenblatt
  MA, et al.
• Presented by Dr. Ivan K. Hsia PGY-3
• September 18, 2006

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Overview

• Purpose of publishing this case report
• How they went about constructing the article
• About the Author(s)
• What they need to get me to believe
• The Case
• Their discussion
• Things lacking in their discussion
• Weinbergs take
• Should this influence our practice?

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Purpose

• They wrote the article to document the first
  successful clinical usage of a lipid emulsion for
  rescue of a patient in Bupivacaine related
  cardiac arrest

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Method

• Not explicitly described in the paper itself
• Case report review of patients chart including
  preoperative status, the anesthetic record,
  literature review of bupivacaine toxicity and the
  use of lipid emulsions for rescue

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Authors Dr. Meg Rosenblatt

• Associate professor of Anesthesiology of Mount
  Sinai School of Medicine NYC
• Expert in Regional Anesthesia
• Director of Orthopedic Anesthesia
• Research interests in improving blood transfusion
  techniques and new regional block methods

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What they need to get me to believe

• 1) make me believe this cardiac arrest was due to
  bupivacaine toxicity
• 2) that it was refractory due to the bupivacaine
• 3) without the lipid infusion the patient would
  not have been successfully resuscitated

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The Case - PreOp

• 58 year old male
• 82 kg, 170 cm, BMI 28.4
• Procedure arthroscopic repair of torn rotator
  cuff (right shoulder)
• PMx CABG _at_ 43 yo, exertional angina with a
  occasional component of rest angina
• Declined further cardiac workup, but deemed
  stable on medical therapy by the cardiologist
• Meds NTG prn, lisinopril, atenolol, clopidogrel
  ECASA held 1 week prior
• Preop EKG RBBB, left ant. hemiblock, evidence of
  old ant. wall MI

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The Case The Regional technique

• Pt arrived to block area, monitors placed with
  stable baseline vital signs 120/80, O2 98 HR 60
  bpm
• 3L O2 via nasal cannula
• 2 mg midazolam and 50 mcg fentanyl via 20g iv LDH
• 50 mm, 22 g Stimuplex insulated needle,
  interscalene groove identified at level of C6
• Brachial plexus identified by eliciting biceps
  stimulation (0.34 mA)
• Injection 20 ml bupivacaine 0.5 and 20 ml
  mepivacaine 1.5, slowly over 2.5 min in 5 ml
  increments without any blood aspirated, pain or
  paresthesias

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The Case The Cardiac Arrest

• 30s after needle removed patient became
  incoherent and developed a tonic-clonic seizure
• 02 delivered via face-mask and 50 mg bolus of
  propofol IV injected, this stopped the seizure
  and spontaneous respirations resumed
• 90s later patient began to seize, 100 mg propofol
  IV given
• Pt. went asystolic, no pulse, ACLS initiated
• 20 mins of ACLS total of 3 mg epinephrine, 2 mg
  atropine, 300 mg amiodarone and 40 U arginine
  vasopressin, monophasic defibrillation escalating
  energy levels of 200, 300, 360 and 360J
• Most rhythms were pulseless v-tach and asystole
• After the 20 mins of unsuccessful resuscitation

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The Case turning point

• As preparations for cardiopulmonary bypass the
  suggestion for the lipid emulsion was made
• 20 Intralipid give as a 100ml bolus
• Continued chest compressions and 1 shock of 360J
• 1 sinus beat returned, then 1 mg atropine and 1
  mg epinephrine given
• In 15 seconds achieved NSR rate 90 bpm
• Infusion started 0.5 ml/kg/min X 2 hours
• Extubated 2.5 hours after arrest

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Discussion

• Scientific evidence that is the foundation of the
  usage of lipids for cardiac arrest rescue in
  bupivacaine toxicity
• Quoted the work of Weinberg et al. regarding the
  rescue of dogs from bupivacaine-induced cardiac
  toxicity with lipids

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Discussion

• Talk about the doses of lipid used and the
  rationale for using larger doses than Weinberg
  had suggested

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Discussion

• Explained how even though the max intravascular
  dosage of 1.2 mg/kg in this case is less than the
  quoted bupivacaine limits of 2.0 mg/kg that it
  could be still toxic
• Quoted a case report in which a pt. also with a
  conduction problem of the heart (1 degree AV
  block) developed arrest after 1.1 mg/kg of
  bupivacaine

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Things not Discussed

• What of the combined effect of mepivacaine?
• Does this make a difference?
• Is there a combined CNS ? CVS effect?

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Things not Discussed

• What about the use of propofol (150mg total) in
  the initial treatment of the seizures?
• The lipid emulsion that propofol is in, was that
  helpful?
• CPS propofol mixed in
• 10 soybean oil
• 2.25 glycerol
• 1.2 purified egg phospholipid

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Things not Discussed

• Or was the propofol harmful?
• Evidence that there are affects from it on the
  cardiac conduction system.

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• Electrophysiological effects of propofol on the
  normal cardiac conduction system.Pires LA,
  Huang SK, Wagshal AB, Kulkarni RS.
• Cardiology. 1996 Jul-Aug87(4)319-24.
• Department of Medicine, University of
  Massachusetts Medical Center, Worcester 01655,
  USA.To determine the electrophysiological
  effects of propofol and to explain the potential
  mechanism(s) whereby it causes bradyarrhythmias,
  10 closed-chest pigs weighing 20-25 kg were
  studied. Each animal was premedicated by
  intramuscular administration of ketamine
  hydrochloride, intubated, and mechanically
  ventilated. Femoral arterial and venous catheters
  were placed, and a comprehensive
  electrophysiologic evaluation was performed at
  baseline and after two doses (1 mg/kg i.v. bolus
  and 0.1 mg/kg/min infusion and an extra 1- mg/kg
  i.v. bolus and 0.2 mg/kg/min infusion) of
  propofol. The electrophysiological effects
  obtained on low-and high-dose propofol were
  compared to baseline values. Propofol caused a
  dose-related decrease in sinus cycle length
  (baseline 565 /- 36 ms, low-dose propofol 541
  /- 28, high-dose propofol 527 /- 26 ms p lt
  0.05), a prolongation of the corrected sinus node
  recovery time (baseline 119 /- 35 ms, low-dose
  propofol 126 /- 32, high-dose propofol 130 /-
  30 ms p lt 0.01), and an increase in the
  His-ventricular interval (baseline 33 /- 4 ms,
  low-dose propofol 36 /- 4, high-dose propofol 40
  /- 3 ms p lt 0.005). All other
  electrophysiological parameters remained
  unchanged, and there were no cases of spontaneous
  atrioventricular block or sinus pauses. We
  conclude that propofol causes dose-related
  depression of sinus node and His-Purkinje system
  functions, but has no effect on the
  atrioventricular node function and on the
  conduction properties of atrial and ventricular
  tissues in normal pig hearts.

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• Frequency-dependent Effects of Propofol on
  Atrioventricular Nodal Conduction in Guinea Pig
  Isolated Heart Mechanisms and Potential
  Antidysrhythmic Properties. Laboratory
  Investigation
• Anesthesiology. 83(2)382-394, August
  1995.Alphin, Robert S. MD Martens, Jeffrey R.
  BS Dennis, Donn M. MD
• Abstract Background The use of propofol has
  been associated with episodes of bradycardias.
  The mechanism(s) underlying these phenomena are
  not well defined. Therefore we investigated (1)
  the chronotropic and dromotropic effects of
  propofol, (2) the frequency-dependent effects of
  propofol on the atrioventricular (AV) node, and
  (3) the physiologic mechanism(s) underlying
  propofol's effects on AV nodal conduction.
• Conclusions We conclude that in the isolated
  guinea pig heart, propofol slows atrial rate and
  depresses AV nodal conduction in a
  concentration-dependent manner. The negative
  dromotropic effects of propofol shows frequency
  dependence and is predominantly mediated by
  M2-muscarinic receptors.

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Things not Discussed

• Potential Harm of Lipid emulsions

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Adverse reactions to lipid infusions

• Frequency not defined.
• Cardiovascular Cyanosis, flushing, chest pain
• Central nervous system Headache, dizziness
• Endocrine metabolic Hyperlipemia,
  hypertriglyceridemia
• Gastrointestinal Nausea, vomiting, diarrhea
• Hematologic Hypercoagulability, thrombocytopenia
  in neonates (rare)
• Hepatic Hepatomegaly, pancreatitis
• Local Thrombophlebitis
• Respiratory Dyspnea
• Miscellaneous Sepsis, diaphoresis, brown pigment
  deposition in the reticuloendothelial system
  (significance unknown)

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Things not Discussed

• Finally, it was 20 minutes into the arrest, could
  the effects have just worn off?
• See Acute toxicity of local anesthetics
  Underlying pharmacokinetics and pharmacodynamic
  concepts (Review article). Reg Anesth Pain Med
  200530553-66

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A Case of Acute Bupivacaine Toxicity

• Prepared conscious adult sheep, to simulate a
  dosage equivalence in humans of about 2mg/kg
• CNS and CVS measures as IV infusion given
• Initially myocardial depression then CNS
  stimulation ? CVS
• Marked ?contractility, ?MAP, ?HR ?CO
• Then convulsions, and disturbed cardiac
  conduction (widened QRS complexes and ventricular
  dysrhythmias
• Without treatment the cardiovascular and CNS
  changes lasted for 20 minutes, when there was a
  sudden return to normal heart rate and rhythm
  the EEG activity returned to normal 40 minutes
  later

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Weinbergs take

• Expert indeed
• Animal studies showing use of lipid emulsions in
  bupivacaine-related cardiac arrest
• Definitely feels that this is a case of rescue in
  a human but understand the limitations of having
  only one documented case
• Says that we should continue to run cardiac codes
  the same, but that 20 lipid solution should be
  available in all hospitals
• States that bupivacaine delays the onset of
  myocardial acidosis and therefore can protect the
  heart during cardiovascular collapse (so if its
  bupivacaine induced arrest dont give up even
  after 20 mins until you tried other things)

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Should this influence our practice?

• 1st case of successful usage of lipid emulsions,
  plausible mechanism for sure, but Im left with
  lots of questions (when to use lipids, how much?)
• Minimal harm for potential great benefit if in
  the situation of cardiovascular collapse
• I think it should be accessible within 15 mins in
  each hospital