This document presents the case of a 43-year-old male who underwent CABG surgery due to significant instent stenosis in his LAD artery. He experienced severe hypotension, ST elevation, and conduction defects post-operatively despite maximal medical and invasive management. The document reviews the pathophysiological effects of cardiopulmonary bypass that may have contributed to his condition, including systemic inflammatory response syndrome and vasoplegic syndrome. It also outlines his critical status in the cardiac ICU and the challenges in managing his circulatory failure, arrhythmias, organ dysfunction, and open sternum.

2. AGENDA
 Case presentation
 Review of literature
 Case progression and outcome
 Conclusion
 Open discussion

3. Case Presentation
 43 years old male patient known to be hypertensive,
dyslipidemic and IHD .
 S/P PCI for LAD 4 months ago in the referring hospital.
 Presented by ACS , coronary angiography revealed
significant instent stenosois in LAD with non
significant lesions in LCX and RCA .
 Patient was hemodynamicaly unstable preoperative
although being on full anti-ischemic measures.
 Laboratory profile is unremarkable .
 Echocardiography showed normal LV function, LVH ,
with apical septal hypokinesia and significant diastolic
dysfunction.

4. Preoperative Medication
 Aspirin
 Plavix
 Statin
 ACE inhibitor
 Nitroglycerin
 Calcium channel blockers
 Heparin infusion

5. Significant dynamic ECG changes

6. Significant dynamic ECG changes & conduction defect

7. Surgical intervention
On bypass CABG offering 2 grafts .
Perioperative major events :
 pre induction sever chest pain followed by ST elevation so urgent sternotomy and
CPB 2 graft were implanted LIMA to LAD & SVG to Diagonal .
 Post off bypass pt. complicated by sever hypotension and still ST segment
elevation occurred on dynamic basis with intermittent conduction defect
necessitate cardiac pacing VVI.
 Revision of grafts and checking the flow showed NAD.
 IABP inserted with escalation of Inotropic support with poor outcome .
 Paroxysmal ST elevation consistent with hypotensive episodes and conduction
defects although full HD supports.
 Bleeding was significantly of concern which was controlled by blood product and
surgical hemostasis

8.  Reccurent attempt of chest closure failed due to
extensive tissue edema and tamponading effects so
skin closed and sternum kept open .
 Follow up ABGs & VBGs showed lactic academia and
the highest lactate was 14 and arterial venous
saturation difference ranging between 25 to 40
 Due to ongoing ischemic events urgent coronary
angiography was requested for reassessment of grafts
and coronaries .

9. Post operative coronary angiography revealed
 Significant stenosis distal to LIMA implantation to LAD
so PCI and stent had being inserted .
 Surprisingly still the patient had ST segment elevation
and conduction defect and the LIMA showed significant
spasm which is partially resolved by Nitroglycerin flush
No more changes in the patient condition with same
paroxysms of ischemic ST elevation and hemodynamic
instability

10.  All invasive intervention measures had been utilized and
still the patient had ST elevation, conduction defect and
hemodynamic decompensation& hypoperfusion .

11. After consumption of all
surgical and cardiac
invasive intervention
weapons it is
NOW
critical care medicine
challenge

12.  Patient referred to CSICU with the following status :
 Epinephrine 0.6 μg /kg /min and norepinephrine 0.5 μg /kg/min
 IABP full augmentation 1:1
 Follow up ABGs showed lactate level more than 15 , PO2/FIo2 consistent
with moderate ARDS ,mixed respiratory and metabolic acidosis .
 Elevated liver enzymes , thrombocytopenia & leukocytosis.
 Rising creatinine consistent with oliguria.
 Pulmonary artery catheter inserted for serial HD parameters follow up :
 SVR 400 to 500 dynes · sec/cm5
 CI 1.9 to 2.6 l/min/m2
 PAWP 14 mmHg
 MAP 40 to 55 mmHg
 RAP 8 to 12 mmHg
 HR 40 to 110 / min
 Still had paroxysmal attacks ST elevation & conduction defects .
 worsening of HD profile consistent with sedation and muscle relaxant
management .

13. Main Pathological challenges
 Vasospasic angina
 Circulatory failure ….????
 Diastolic heart failure & conduction defects
 ARDS.
 Organs dysfunction.
 Open chest with high incidence of wound sepsis

15. Target Directed
Therapy
&
Drug pathology
interaction
Circulatory
support &
Vasoplegic
syndrome
management
Pulmonary
Management
Upgrading of
cardiac pacing
to DDD
bedside
Vassospastic
angina mangment
(modified triple H
therapy ?!)
Wound sepsis
prophylaxis &
organs support
management
Sedation
analgesia
management

16. CARDIOPULMONARY BYPASS
&
VASOPLEGIC SYNDROM

17. Cardio-Pulmonary Bypass
 The use of the cardiopulmonary bypass (CPB) machine during
cardiac surgery has become a widely employed practice.
 Although CPB simplified cardiac surgery , it had also major
adverse effects on a patient’s body organs .
 These include complications of the immune system, heart,
lungs, kidneys, and brain and physical harm.

18. Pathophysiological effects of CPB
The Negative Effects of the Cardiopulmonary
Bypass: SIRS activation
 Once the inflammatory response is activated,
the body releases many different components.
Complement is one of these inflammatory
components that consists of several different
elements. Two of these, C5a and C3a, show to
be significantly elevated after CPB .
 Cytokines, such as tumor necrosis factor
(TNF) and several of the interleukins (IL), as
IL-8 and IL-6 are also a major component of
the inflammatory response that may be
increased (Laffey et al., 2002).
 Other elevated inflammatory components
due to CPB include monocytes, neutrophil ,
and leukocyte activation .
All the above reactions interact to hit the
endothelial system , release Oxygen free radicle ,
activation of platlets andd malignant production
of nitic oxide and arachidonic acid metabolism

19. Pathophysiology of CPB
 Approximately 20% of low-risk patients develop complications
following CPB (Laffey et al., 2002)
 Once the endothelium of the microcirculation is malfunction,
its surface becomes more susceptible to activated platelet with
subsequent microcirculatory failure with excessive production
of NO resulting impairment of tissue perfusion .
 The generalized inflammatory process contributes to multi-
organ failure or dysfunction (Laffey et al., 2002) when proinflammatory
mediators are elevated relatively to antiinflammatory
mediators (Cremer et al., 1996).

20. Pathological effect of CPB
These systemic inflammatory immune response participate in
all complications post CPB including
 Pulmonary dysfunction, (Atelectasis, ALI, ARDS,PHTN, Effusion )
 AKI ,
 Neurological (structural or functional )
&
 Hemodynamic decomposition by different presentation

21. VASOPLEGIC SYNDROME
Vasoplegic syndrome (VS) is an integration of adverse effect of
general anesthesia and / or cardiopulmonary bypass in potential high
risk patients expressed as refractory hemodynamic decompensation
to fluid and vasopressor resuscitation manifested by :
 Low SVR < 700dynes · sec/cm5 during intravenous norepinephrine
infusion more than 0.5 μg/kg/ min
 Cardiac index >2.5 L/min/m2 ,
 Mean Arterial blood pressure <50 mmHg,
 Right atrial pressure <5 mmHg,
 Left atrial pressure <10 mmHg

22. VASOPLEGIC SYNDROME
The incidence of VS in cardiac surgical patients is 8% to
10 %, but may increase up to 50% of so sick patients
preoprativly & those who were taking renin-angiotensin
system (RAS) antagonists.
 In cardiac surgical patients with persistent hypotension
in the postoperative period, the associated mortality
approaches 25% to 40%
It can be also associated with, severe sepsis, anaphylaxis
and hemodialysis

23. Predisposing Factors of VS
Independent risk factors for post-operative VS
 Pre operative Intravenous heparin association up to 55.6%
 Pre operative renin-angiotensin system (RAS) antagonists up to 44.4 %
 Pre operative Calcium channel blockers up to 47.2%
Other Risk factors (Exhaustion of Catecholamine Drive and Immune dysfunction )
 Beta-blockers,
 Protamine use,
 Myocardial dysfunction,
 Diabetes mellitus,
 Heart transplant,
 Higher added EuroSCORE,
 Pre-cardiopulmonary bypass (CPB) hemodynamic instability,
 Valvular and Heart Failure Surgery,
 Long duration of CPB,
 Ventricular assist device insertion

24. Pathogenesis of V.S.
CPB mediated mechanism through:
 Cytokine and inflammatory mediators .
 Endothelial injury.
 Nitric oxide-mediated smooth muscle relaxation.
 Catecholamine receptor down regulation.
 Cell hyperpolarization.

25. Pathogenesis
Nitric Oxide synthesis and Guanylate Cyclase activation and
its action on vascular smooth muscle play a corner stone in
pathogenesis of VS.
Nitric oxide is produced by two types of nitric oxide
synthase:
 A constitutive type
&
 An inducible type.
The inducible synthase is produced in vascular smooth-muscle
cells, cardiac myocytes by different inflammatory mediators

26. Nitric
Oxide
• nitric oxide
synthase:
• A constitutive type
• &
• An inducible type
Gaunylat
Cyclase
cGMP
• Vascular
Dilatation
• Myocardial
suppression
IL1 & OFR
• CPB mediated
inflammatory
response
Gaunylat
Cyclase
cGMP
• Vascular
Dilatation
• Myocardial
suppression

27. Pathogenesis
Under normal physiologic circumstances, blood pressure is
maintained via three integrated systems :
 The sympathetic system (Major role ).
 The renin-angiotensin system
 The Vasopressinergic system (minor role ) .
Sympathetic Nervous
System
Renin Angiotensin
system
Vasopressinergic
system

28. Pathogenesis
 Most anesthetic drugs reduce the influence of the sympathetic
system on cardiovascular tone with dependence on RAS and
vasopressinergic system .
 RAS antagonists such as angiotensin converting enzyme inhibitors
(ACEIs) and angiotensin receptor blockers (ARBs) block the RAS
response to hypotension.
 Endogenous release of vasopressin (AVP) occurs to compensate
for the blockage of both the RAS and the sympathetic nervous
system, but this is not resolve the hypotension due to its low
concentration secondary to depletion of neurohypophyseal stores of
vasopressin after profound osmotic stimulation and after sustained
baroreflex stimulation .

29. Types of Vasoplegic Syndrome
Catecholamine Sensitive
 Catecholamine Resistant

30. The Rational Of Management
 Early suspicion and prediction specially in combined
presentation with other illness ….TIME IS LIFE
 Early intervention (to diagnose and to treat )….
 Pharmacological therapy ……….a lot of debate
 Aggressive management………..
 Perfusion Directed Therapy…….
 Dedicated meticulous monitoring( HD profile ,
pulmonary function , renal function
,neuropsychiatric status , hematological status ,
infection and sepsis and others )
 Management of associated problems

31. Critical Care Management
Fluid resuscitation for optimizing filling pressures(GDT)
Vasopressors
Norepinephrine: mostly will be resistant (receptor mediated
resistance )
Vasopressin: caused significant increases in mean arterial
pressure and systemic vascular resistance, and resulted in a
marked reduction in norepinephrine doses, without
considerable changes in cardiac index. the efficacy of
vasopressin in clinical scenarios in which catecholamine are
ineffective with consideration of serious side effects of
aggravating mesenteric ischemia and reduction of urine
output that may limit its usage
????????????????????????????

32. Methylene Blue
 Generaly It is approved for oral and intravenous administration in
the setting of methemoglobinemia, and as a surgical tracer dye for
detection of fluid leak.
 It is available as a solution 10mg/ml, its oral absorption ranges from
53-97%,
 It is eliminated in bile, feaces and urine as leucomethyle blue.
 It is used in all age groups
 The onset of the hemodynamic effects of methylene blue
is relatively rapid

33. Evidence in post-operative use
 Methylene blue has predominantly been used to reverse
vasoplegia in a post-operative setting. Several groups of
studies have shown that the post-operative administration of
a single dose of MB in VS can restore SVR.
 Kofidis et al had being demonstrated successful use of MB
for vasoplegia in a post-transplant patient

34. Evidence in post-operative use
 Levin and colleagues randomized 56 patients with vasoplegia to receive IV
MB (1.5 mg/kg over 1-h) or placebo. There were no deaths in the MB
group and six deaths (21.4%) in the placebo group.
 Methylene blue reversed vasoplegia in about 2 h, while in those treated
with vasopressors (28.6%) only, vasoplegia persisted for more than 48 h
with progression to MOFS .

35. Intra-operative use of MB
 Grayling and Deakin added MB to the pump prime as treatment
for septic endocarditis during a valve operation, and followed
this up with a post-operative infusion.
 Evora and colleagues reported that CPB had to be re-instituted,
following a severe protamine reaction while during CPB, they
were unable to increase arterial pressures even with
norepinephrine and had to use an infusion of MB to generate
adequate pressures.

36. Pre-operative use
 Study done by Ozal and associates identified 100 patients for
coronary surgery who were at high risk for vasoplegia
(preoperative ACE inhibitors, calcium blockers, and heparin) and
randomized these patients to receive methylene blue (2 mg/ kg
over 30 min) or placebo pre-operatively.
 The prophylactic infusion of MB in these patients was associated
with a higher SVR during surgery (compared to placebo) and a
lower requirement for norepinephrine, inotropic support, fluid and
blood transfusions.
 While prophylactic MB prevented VS in every patient in whom it
was administered, 26% of the patients in the placebo group had
VS.

37. Methylene Blue
Mode of action on vascular smooth muscle:
Methylene blue counteracts the effect of NO and
other vasodilators on the endothelium and vascular
smooth muscle and it is believed to act competitively
with NO, by binding to iron heme-moiety of soluble
guanylyl cyclase (sGC) and blocking sGC action in
vascular smooth muscle alleviates the vasorelaxant
effect seen in VS.

38. Nitric
Oxide
• nitric oxide
synthase:
• A constitutive type
• &
• An inducible type
Gaunylat
Cyclase
cGMP
• Vascular
Dilatation
• Myocardial
suppression
IL1 & OFR
• CPB mediated
inflammatory
response
Gaunylat
Cyclase
cGMP
• Vascular
Dilatation
• Myocardial
suppression
Methylen blue

39. Methylene Blue
Dose:
 Single dose of i.v. MB 1-2mg/Kg over 20 minutes infusion
time as rescue treatment in the setting of vasoplegia post
cardiac surgery.
 Continuous MB infusion is described in the patient who is
not responding to a single dose of MB and is administered
for a variable length of time, 120mg MB diluted in D5W
given over 1-6 hours .
 Methylene Blue has been used in the setting of vasoplegia
related to cardiac surgery, sepsis , anaphylaxis, liver failure
and hemodialysis .
 At higher doses than that described above, MB becomes an
oxidant which oxidize hemoglobin resulting in
methemoglobinemia and hyperbilirubinemia

40. Contraindications and side effects of Methylene Blue :
 MB should not be used in patients who are hypersensitive to the
drug.
 Although contraindicated in patients with severe renal
insufficiency, it can be used in hemodialysis dependent patients .
 MB must be used cautiously in patients with either Glucose-6-
Phosphate dehydrogenase deficiency because of the risk of
hemolytic anemia .
 Rare side effects with high doses include cardiac arrhythmias
(nodal rhythm or ventricular ectopy), coronary vasoconstriction,
and angina, decreased COP, decreased renal and mesenteric
blood flow, increase pulmonary vascular resistance and
worsening gas exchange .

41. Summary as regards Methylene blue
1) In the recommended doses it is safe (the lethal dose is 40 mg/kg);
2) The use of MB did not cause endothelial dysfunction.
3) MB is not a vasoconstrictor, but it facilitate the catecholamine
vasoconstrictor effect and eradicate the effect of vasodilatory substances
4) The most used dosage is1- 2 mg/kg as IV bolus followed by the same
continuous infusion because plasma concentrations strongly decays in the first 40
minutes.
5) Although there are no definitive multicentric studies, the MB used to treat
heart surgery VS, at the present time, is the best, safest and cheapest option, but;
MB ACTION TO TREAT VASOPLEGIC SYNDROME IS TIME-DEPENDENT”.

42. Other lines of treatment
 Fluid resuscitation
 IV corticosteroid
 Treatment of complication ( MOFS management )

43. Vasoplegic Syndrome complicating other illness
increases management chalanges(diagnosis & treatment )
 Vasoplegic syndrome in patient with Vasospastic
angina .
 Vasoplegic syndrome in patient cardiomyopathic
patient with poor EF .
 Vasoplegic syndrome in patient ALI & ARDS .
 Vasoplegic syndrome in patient Acute right sided
failure .
 Vasoplegic syndrome in patient AKI.
 Vasoplegic syndrome in patient with mechanical
circulatory support .

44. What about our sick patient ??

45. Day zero Post Operative
 Optimization of filling pressure with IV fluid.
 Single bolus dose of M.B 100 mg followed by infusion for 6
hours beside NEPI & EPI infusion
 Significant improvement of SVR progressively increased to
900 - 1300 dynes · sec/cm5 on follow up with MAP 70 to 80
 Upgrading of pacing to DDD
 Mechanical Ventilatory management following the
protective lung strategy and titrating PEEP to achieve good
O2 saturation
 No more ST elevation as if MAP above 70
 Sedation/muscle relaxant :Ketamine and pancuronium Pavulon.
 Adjusted doses of prophylactic antibiotics

46. Day one post oprative
 Better HD profile
 Better serial ABG
 Better pulmonary artery catheter hemodynamic
parameters .
 Bedside ECHO showed good LV function
 Weaning of IABP then DC .
 Improvement in laboratory profile
 Starting Weaning vasopressors and inotropic supports.
 Better ventilator outcome.
 Good urine output with good negative balance .

47.  Sternum closed on 3rd day P.O.
 Patient continued progressive improvement of all
pathological parameters and extubated on 6 th day post
operative.
 Normalization of laboratory profile follow up.
 kept transiently on NIV ad CPT due to segmental lung
collapse .
 Patient discharged from CSICU after total 14 days to
intermediate care unit for 2 days then to regular inpatient
section .
 Still had intermittent conduction defect so PPM was
planned pre discharge .
 Infrequent ST elevation on follow up(Prinzmetal's angina )
kept on Ca channel blocker life long

48. Conclusion
 Vasoplegic syndrome occurs in 8—10% of patients following cardiac
surgery and is associated with increased morbidity and mortality. In a
subset of patients with profound vasodilatation, VS does not response
to fluids and conventional vasoconstrictors.
 In patients who are catecholamine resistant , the early use of
vasopressin is beneficial and in some centers vasopressin is rapidly
replacing noradrenaline as the first line treatment for vasoplegic
syndrome with consideration of its availability & major side effects .
 The inhibition of guanylate cyclase elicited by nitric oxide or any
endothelially soluble guanylate cyclase-activating factor (e.g.
interleukin-1, atrial natriuretic peptide, and bradykinin) could be a
great effective approach in the treatment of norepinephrine-
refractory vasoplegia after CPB, and forms the basis for the use of
methylene blue.

49. Conclusion
 Methylene blue seems to be a potent approach to norepinephrine
refractory vasoplegia with no major side effects. The early use of
methylene blue may halt the progression of low SVR even in patients
responsive to norepinephrine and mitigate the need for a prolonged
vasoconstrictor use.
 Preliminary results suggest that pre-operative methylene blue reduces the
incidence and severity of vasoplegic syndrome in high-risk patients, thus
ensuring adequate SVR intra and post-operatively.
 Whether methylene blue should be the first line of therapy in patients
with VS is a matter of debate and should be tailored according to the
patient statues .
 There is inadequate evidence to support its usage as a first line drug,
although the promising results of the small number of studies .
 On the basis of the current evidence methylene blue does not appear to
be the ‘magic bullet’ which need further studies . .

50. When we are stuck we must make our way
of thinking out of the box in a safe manner