Anesthesia Considerations for Simultaneous Pancreas-Kidney Transplantation and Post-Reperfusion Syndrome: A Case Report and Review of the Literature

1
Anesthesia Considerations for Simultaneous
Pancreas-Kidney Transplantation and
Post-Reperfusion Syndrome A Case Report and
Review of the Literature

• Christopher J. Patton, BSN
• Barnes-Jewish College

2
CASE STUDY
3
REPEAT SPKT

• 43-year-old, ASA 3, 158 cm, 47 kg female
• Underwent primary SPKT two years earlier
• Pancreatic graft failure due to severe
  pancreatitis
• Renal graft failure secondary to rejection
• Medical History IDDM, ESRD, anemia, GERD, HTN,
  HLD, IBS
• Anesthesia History Unremarkable
• Allergy Cephalexin (rash)

4
PREOPERATIVE ASSESSMENT

• Airway Mallampati III, TM Distance 5 cm,
  Normal Cervical Extension
• Hypertensive MAPs as high as 125 mm Hg noted
• ECG NSR with poor R-wave progression
• Recent nuclear stress test Negative
• TTE Normal LVEF, mild LVH/LAE, trace MR/TR
• CXR Remarkable for an in situ left subclavian HD
  catheter with its tip at the atriocaval junction

5
PREOPERATIVE ASSESSMENT

• Lungs CTA Bilaterally
• Heart Tones Normal
• No Carotid Bruits
• Labs
• Elevated Cr and PO4 (4.43/6.0 mg/dL,
  respectively)
• Decreased H H (9.9/28.8 g/dL)
• Severe N/V three episodes of emesis in the
  holding area
• Treated with transdermal scopolamine, two doses
  of odansetron, famotidine, and metoclopramide
• Midazolam 2 mg administered prior to leaving
  holding

6
INDUCTION
7
MAINTENANCE OF ANESTHESIA

• Desflurane titrated between 4.2-6.5 inspired
  concentration in equal mixture of oxygen and air
• NMB maintained with atracurium totaling 160 mg
• Piperacillin/Tazobactam 2.25 g per surgeon
  request
• Serum glucose assessed Q30 minutes and regular
  insulin administered IV in small doses throughout
  the case per the surgeons request (9 units
  total)

8
INITIATION OF IMMUNOSUPPRESSIVE THERAPY AND
INITIAL HYPOTENSION

• Immunosuppressive therapy induced with
  methylprednisolone 350 mg IV (Over 15 min)
• Followed by a continuous infusion of
  anti-thymocyte globulin (ATG) 4.1 mg/hr
• Infusion decreased to 2 mg/hr after
  hypotension noted
• Small boluses of phenylephrine, calcium
  chloride and ephedrine to maintain MAP 80 mm Hg
  
• BP stabilizes with 1.5 L of 0.9 NS, 250 mL of
  5 albumin, and dopamine infusion at 5 ?g/kg/min

9
WERE CRUISING

• Prepare for pancreas graft insertion
• Heparin 3,000 units
• Mannitol 12.5 g
• Graft inserted
• Vascular anastamoses completed
• Surgeon announces venous clamp will be released
• Student experiences SEVERE pudendal neuropathy as
  this happens..

10
PANCREATIC GRAFT REPEFUSION

• Within 5 min, MAP acutely decreased from
  a pre-reperfusion value of 79 mm Hg to
  28 mm Hg, and heart rate increased to
  approximately 140 beats per minute
• The ATG infusion paused and sodium bicarbonate 1
  ampule, calcium chloride 500 mg, phenylephrine
  400 ?g, ephedrine 10 mg, norepinephrine 64 ?g,
  and epinephrine 200 ?g, were all administered IV
  over the next 5 minutes before the MAP recovered
  to 60 mm Hg
• One unit of packed red blood cells infused and
  continuous infusion of norepinephrine 0.05
  ?g/kg/min was initiated and quickly titrated to
  0.2 ?g/kg/min

11
Over the next 80 minutes

• Norepinephrine infusion titrated to 0.25
  ?g/kg/min
• An additional six 64 ?g boluses of norepinephrine
  were administered
• 2L 0.9 NS bolused to maintain a MAP gt 60 mm Hg
• Remember, goal MAP 80 mm Hg
• Diphenhydramine (25 mg) and esmolol (10 mg) also
  administered with no observed response
• Heart rate remained 120 140 bpm
• About four hours into the case, MAP stabilized at
  70 mm Hg
• Per the surgeons request, 2,000 units of heparin
  administered prior to clamping for vascular
  anastamoses of renal graft
• 12.5 g mannitol administered prior to reperfusion
  of renal graft
• Anesthesia grimaces.

12
RENAL GRAFT REPEFUSION

• Upon reperfusion of renal graft, MAP again
  acutely fell from 72 mm Hg to 51 mm Hg
• A norepinephrine 128 ?g bolus administered and
  second unit of PRBCs transfused
• Furosemide 10 mg also administered, per the
  surgeons request
• CardioQ SV monitor (Deltex Medical, Greenville,
  SC) utilized to assess fluid status
• 4.5 L of crystalloid infused over remainder of
  case, per fluid optimization protocol
• In total, patient received 8 L crystalloid and
  approximately 1.5 L colloid
• Estimated blood loss was 500 mL
• A total of three ampules of sodium bicarbonate
  were administered to correct acidosis

13
EMERGENCE

• By the end of the case, hemodynamics stabilized
• Norepinephrine infusion decreased to 0.08
  ?g/kg/min
• Dopamine infusion discontinued
• ATG infusion reinitiated at full dose
• Neuromuscular blockade was antagonized with
  glycopyrrolate 0.5 mg and neostigmine 3.5 mg
  after surgical incision closed (fascia left open)
  
• Patient awoke and followed commands, but was
  determined to be too weak to safely extubate
• Propofol infusion initiated and patient
  transported to ICU in stable condition

14
POSTOPERATIVE COURSE

• Patient was extubated the following morning and
  transferred out of the ICU two days later
• Eight days after SPKT, patient returned to OR for
  closure of fascia
• Wound infection and edematous pancreas with
  multiple necrotic areas discovered
• Four days later, returned OR for ID of the
  abdomen, debridement of several small necrotic
  areas on the pancreas, and closure of the fascia
  and skin
• Patient remained hospitalized for a month prior
  to being discharged to a rehabilitation facility

15
DISCUSSION
16
WHO BENEFITS FROM SPKT?

• Approximately 50-60 of insulin-dependent
  diabetics develop diabetic nephropathy, the
  leading cause of renal failure requiring
  hemodialysis (HD) in young and middle-aged adults
  in the United States (US).1,2
• While pancreatic transplantation may be indicated
  for the treatment of disease states such as
  pancreatitis or cancer, an overwhelming 96 of
  the total pancreatic transplants in the US are
  performed in patients with underlying IDDM.3,10

17
WHY SPKT?

• SPKT is curative treatment for both IDDM and
  ESRD
• SPKT has become far more prevalent over the past
  40 years2,3,10

18
WHAT HAPPENS WHEN SPKT FAILS?

• Uncommon
• Serious
• Few institutions with much experience

19
PANCREATIC ANASTAMOSES

• Bifurcation of donor Iliac Artery anastamosed to
  Superior Messenteric and Splenic Arteries during
  bench preparation of pancreatic graft to improve
  ease of anastamosis to recipients Right Common
  Iliac Artery during transplantation

20
RENAL ANASTAMOSES
21
ANESTHESIA CONSIDERATIONS

• Preoperative Assessment, Planning Collaboration
• Minimizing Consequences of IDDM and ESRD
• Glycemic Control
• Autonomic Neuropathy
• Avoidance of Drugs with Renal-Dependent
  Metabolism
• Fluid Management
• Management of Immunosuppressive Therapy
• Optimization of Graft Function
• Commonly Utilized Intraoperative Drugs
• Ensure Adequate Graft Perfusion
• Appropriate Fluid/Pressor Management
• Management of Post-Reperfusion Syndrome (PRS)

22
PREOPERATIVE ASSESSMENT

• Begins with a review of the health history, with
  special attention to co-existing diseases that
  often accompany ESRD and IDDM
• Hypertension, anemia, uremia, and cardiac
  disease11
• CXR, ECG, echocardiography and stress testing
  warranted in most patients due to risk for silent
  ischemia secondary to autonomic neuropathy9,10

23
PREOPERATIVE LABORATORY STUDIES

• Laboratory tests should include CBC, CMP,
  hemoglobin A1C, coagulation studies, and a TC
  for at least two units of washed PRBCs8,11
• The transplant workup will also include screening
  test for a multitude of infectious diseases, as
  well as ABO and human leukocyte antigen (HLA)
  compatibility11

24
PREOPERATIVE EXAM

• Primary concerns cardiopulmonary system and
  airway
• VS, orthostatics, and dialysis details facilitate
  estimation of blood volume status9
• Difficult airway?
• Few studies propose intubation difficult in
  diabetics
• Subsequent studies did not substantiate these
  fears2
• Nonetheless, prudent to assess joint mobility in
  neck and jaw and to prepare for difficult
  visualization of laryngeal structures12
• Identify HD shunts/fistulas and verify adequate
  padding, as pressure may cause thrombosis2,8

25
GLYCEMIC CONTROL

• Many proposed management strategies
• Most authors agree BG should be assessed at least
  Q30-60 minutes and treated with IV regular
  insulin
• Avoid complications such as ketoacidosis,
  depressed immune function, decreased wound
  healing, and risk for significant neurologic
  insult in the setting of cerebral
  ischemia.2,6,8,12
• Keep BG gt 150 mg/dL prior to pancreatic graft
  insertion
• Glucose concentrations decrease 50 mg/dL/hr
  after reperfusion
• Hypoglycemia difficult to detect due to decreased
  autonomic from anesthesia and diabetic and renal
  disease-related neuropathy2,8
• Another complicating factor is routine
  administration of high-dose corticosteroid for
  immunosuppressive therapy

26
ANESTHETIC TECHNIQUE

• Regional anesthesia has been successfully used
  for SPKT in a small number of reported cases
• Most authors encourage general endotracheal
  anesthesia2,6,8,12 for the following reasons
• The long, tedious nature of these surgeries
• The benefit of muscle relaxation
• The potential for hemodynamic instability
• Furthermore, splanchnic perfusion to the
  transplanted organs is a major concern and the
  sympatholytic effect of regional anesthesia may
  pose a danger to adequate graft perfusion2,8

27
IMMUNOSUPPRESSIVE THERAPY

• Transplant function dependent on
  immunosuppression
• Induction Agents Started at time of
  transplantation
• May continue for a few doses while maintenance
  agents initiated
• Maintenance Agents Will be continued
  indefinitely
• Commonly encountered induction regimens include
  either monoclonal or polyclonal antibodies which
  may be supplemented with a large dose of
  corticosteroid6,10
• Regimens vary between patients and institutions
• Imperative that anesthetist clarifies schedule
  and dosing with transplant team6

28
SIDE EFFECTS
Millers Anesthesia, 7th ed., 2010
Clinical Anesthesia, 6th ed., 2009
29
AUTONOMIC NEUROPATHY

• Diabetics, especially those with ESRD, prone to
  autonomic neuropathy that may cause2
• Gastroparesis increases risk for
  aspiration1,7,8,12,13
• Cardiovascular lability possible intraoperative
  hypotension requiring pressors, dysrhythmias, and
  bradycardia resistant to atropine1,12,13
• Regardless of volume status, patients with ESRD
  often experience exaggerated hypotension with
  induction of anesthesia1,9

30
INDUCTION OF ANESTHESIA

• No standard induction drugs specifically
  contraindicated
• All patients presenting for SPKT should be
  considered at risk for aspiration
• RSI with cricoid pressure and slight reverse
  trendelenberg positioning indicated2,6,8

31
NEUROMUSCULAR BLOCKADE

• Succinylcholine usually safe in patients with
  ESRD
• Serum potassium should be lt 5.5 mEq/L
• 0.6 mEq/L increase in serum potassium after
  intubating dose of succinylcholine2,8,14
• CAUTION risk for hyperkalemia after
  succinlycholine administration may be increased
  in patients with motor and sensory neuropathy
  secondary to diabetes and uremia12
• Alternative to succinylcholine for RSI is
  rocuronium
• Subsequent doses should be carefully titrated
  based upon train-of-four monitoring with a
  peripheral nerve stimulator2,6,8
•  Cisatracurium and atracurium ideal due to
  extrarenal metabolism via Hoffman degredation and
  plasma cholinesterase2,6,8,11,14
• Primary metabolite, laudanosine, may cause
  seizures via stimulation of CNS at high plasma
  concentrations9

32
MAINTENANCE OF ANESTHESIA

• Balanced anesthetic technique likely best method
  to sustain hemodynamic stability2
• Drugs selected based upon known side effects9
• N2O often omitted
• Morphine and meperidine should also be avoided
  due to the action of their metabolites2
• Desflurane and isoflurane are commonly used
  inhaled anesthetics2
• While the metabolism of sevoflurane has been
  implicated in nephrotoxicity, there is a lack of
  evidence clearly substantiating these concerns

33
FLUID CHOICES

• Multiple considerations
• Electrolyte Balance
• Edema/Third-Spacing
• Acid-Base Balance
• Which Crystalloid?
• NS vs. LR vs. Plasmalyte?
• NS widely used, but LR and Plasmalyte may be
  better
• Which Colloid?
• Albumin vs. HES Solutions?
• Albumin demonstrated to be best colloid

34
MONITORING

• Standard ASA monitors placed upon entering OR
• HD catheters may be used if CVC access warranted
• CVP 10 15 mm Hg optimizes CO/Renal Blood
  Flow2,6,8
• Pulmonary Artery Catheter based upon HP
• Higher filling pressures (gt20/15 mm Hg)
  indicative of better graft function than lower
  pressures in one study2
• A-Line based upon HP
• Non-invasive cardiac stroke volume monitors
• These have been found to facilitate goal directed
  fluid therapy
• Demonstrated to PONV, morbidity, and hospital
  stay15

35
INTRAOPERATIVE HEMODYNAMICS

• Moreover, despite the anesthetists best efforts,
  major hemodynamic shifts are common during organ
  transplantation
• One illustration of these hemodynamic shifts was
  provided by a large series that found substantial
  changes in intraoperative hemodynamics, with
  hypotension more likely than hypertension (49.6
  vs. 26.8)6

36
SPKT HEMODYNAMICS CONTINUED

• Another study followed 17 patients presenting for
  SPKT reported similar hemodynamic shifts4

37
POST-REPERFUSION SYNDROME

• PRS was first described by Aggarwal (1987), in
  the context of orthotopic liver transplantation
  (OLT)
• A systemic phenomenon generally defined as a 30
  decrease in MAP, sustained gt 1 minute, occurring
  lt 5 minutes after organ reperfusion5,20-22
• PRS has been reported in surgeries other than OLT
• Cardiopulmonary bypass, aneurysm repair, ischemic
  limb reperfusion, and intestinal and renal
  transplants
• Literature describing incidence of PRS is
  inconsistent, with rates between 20-55 of all
  OLT patients and 4 of renal transplants
  reported5,20

38
PRS PHYSIOLOGY

• While the exact mechanism of PRS remains
  controversial, some of the initially proposed
  causes included
• Cold preservation solution into systemic
  circulation20
• Acid-base and electrolyte derangements20,21
• Release of pro-inflammatory mediators, including
  nitric oxide (NO), due to massive induction of
  oxidative stress21
• However, one prospective study found no
  statistical correlation between serum pH, core
  temperature, potassium and calcium levels, or
  arterial blood-gas tensions and PRS5
• In the same study, a decreased SVR was the only
  variable that correlated significantly with PRS.

39
PRS PHYSIOLOGY CONTINUED

• Another study exploring PRS hemodynamics found
  preload in PRS patients was significantly lower
  than non-PRS patients
• Despite equal LV function, as observed by TEE
• Thus, acute vasodilation could explain both the
  decrease in SVR and preload
• This phenomenon may be mediated by the release of
  vasoactive inflammatory mediators, secondary to
  an immunogenic response, resulting in a massive
  extracellular fluid shift
• Supported by another study that identified
  increased levels of neutrophil and macrophage
  activation, with simultaneous anaphylatoxin
  formation, in patients experiencing PRS5
• Another proposed mechanism is the release of
  ROS2,6

40
WHY IS PRS IMPORTANT?

• PRS implicated in a number of undesirable
  outcomes
• Longer mechanical ventilation times and ICU
  stays, poor graft function, acute organ
  dysfunction unrelated to the surgical site, and
  increased mortality5
• One study examining PRS in renal transplant
  patients found the rate of graft failure at six
  months was increased by 10 in patients
  experiencing PRS
• Additionally, the number of post-transplant
  hospitalization days was almost twice that of
  non-PRS patients who had the same surgery
• Another study, following OLT patients who
  developed PRS, reported the relative risk of
  severe kidney dysfunction to be over three times
  greater that the non-PRS group
• More frightening, the relative risk of death was
  determined to be almost three times greater than
  non-PRS cohorts

41
WHO IS AT RISK FOR PRS?

• In the previously referenced study examining
  PRS in renal transplant patients, a significant
  correlation was identified between PRS and
  patients who were either diabetic, Asian, older
  than 60, or transplanted with an organ from an
  extended criteria donor (ECD)5

42
PRS AUTONOMIC DYSFUNCTION

• A separate study reported an increased prevalence
  of PRS in patients with autonomic dysfunction
• As previously discussed, both IDDM and ESRD are
  associated with autonomic dysfunction23
• Thus, these pathologies may be good markers for
  predicting PRS in surgical patients.

43
PRS TREATMENTS?

• Unfortunately, there does not yet appear to be a
  consensus in the literature regarding effective
  treatment regimens for PRS
• Proposed strategies include2,5-8,11,12,20,21
• Methylene Blue to inhibit inducible NO synthase
  and scavenge NO
• On retrospective study of 700 patients found
  methylene blue to have no effect on changes in
  MAP, vasopressor or blood transfusion
  requirements, or end-organ effects
• Prophylactic administration of epinephrine and
  atropine to attenuate hypotension and bradycardia
• Mannitol to scavenge ROS
• Sodium bicarbonate to buffer the increased acid
  load
• Nonetheless, despite 25 years of research, there
  remains much to learn about PRS
• However, as more definitive explanations of the
  mechanism and treatment of PRS emerge, it is
  reasonable to expect outcomes for a number of
  surgical procedures to improve

44
HINDSIGHT IS 20/20
45
AREAS FOR IMPROVEMENT

• More proactive/aggressive treatment of N/V
• Haldol/droperidol, diphenhydramine, etc
• Tighter glycemic control
• Continuous insulin infusion
• Earlier utilization of SV Monitor
• Aggressive treatment of early PRS with Epi?
• Fluid Selection
• LR only or more balanced ratio of LR/NS

46
THANK YOU!
47
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