2. A 73-year-old lady had a kidney transplant 19 years ago. Her current serum creatinine (S Cr) is 352 µmol/L. She also has a metallic mitral valve (she is on warfarin with INR 3.5). This lady presented with severe LIF pain and tenderness. Non-contrast CT showed diverticular perforation of sigmoid colon. Currently she is on azathioprine 100 mg/d and steroids. The surgeon decided to perform Hartmann’s procedure.

  • How do you manage this lady?
  • Post-operatively, she developed sepsis, how do you manage her immunosuppression?
 
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AMAL Anan
AMAL Anan
3 years ago

How do you manage this lady?
High risk patient high risk of bleeding and advanced kidney disease,
Blood cultures and start broad spectrum antibiotics
Fresh frozen plasma plus unfractionated heparin
Pre-operative cardiac evaluation
And restart warfarin after 2days
For immunosuppressant, Continue azathioprine and give steroids 100mg hydrocortisone and oral Prednisone after 2 days postoperative
Cardiac follow up by TEE
Post-operatively, she developed sepsis, how do you manage her immunosuppression?
If emergency stop azathioprine and explain to patient about he may loss his graft if infection can be treated decrease dose of azathioprine and shift to tacrolimus if patient improved

Ibrahim Omar
Ibrahim Omar
3 years ago

1- How do you manage this lady?

  • this is a high-risk patient with an expected high mortality. full explanation should be offered and informed consent should be signed.
  • the usual peri-opeartive care should be followed plus the following :

1- doubling steroid dose for few days and changing oral prednisolone to IV hydrocortisone with the equivalent doubled dose of Prednisolone (1 mg of prednisolone = 4 mg of Hydrocortisone)
2- adequate cover with IV anti-biotic combinations.
3- avoid nephrotoxics & intra-operative hypotension.
4- adequate IV fluids and serial kidney functions.
5- involvement of an experienced nephrologist.

2- Post-operatively, she developed sepsis, how do you manage her immunosuppression?

  • holding Azathioprine
  • continuing IV hydrocortisone.
Balaji Kirushnan
Balaji Kirushnan
3 years ago
  • How do you manage this lady?

this patient is an elderly lady with a history of kidney transplant 19 years ago. she currently has graft dysfunction with a creatinine of 3.5mg%. she also has metallic prosthetic valve in the mitral area. She is on warfarin with an INR of 3.5. She has presented with acute abdomen due to diverticular perforation1. Management of the patient has many aspects to it

  1. Immediate resuscitation: Patient needs to get a basic workup done with complete blood count, liver function tests, renal function tests, aPTT, Blood culture. She needs to be started on IV fluids if hypotensive and transfuse PRBC if there is severe anemia (Hb<5gm%).
  2. IV antibiotics namely 3rd generation cephalosporins and IV metronidazole to cover gut anaerobes are needed as an emergency basis after sending cultures. She needs to be transfused with FFP urgently of even PCC (prothrombin complex concentrate) if available.
  3. patient should be kept NPO
  4. Family and the patient should be counselled for high risk surgery with ICU monitoring and sepsis observation. In view of severe graft dysfunction pre existing to the admission, counselling about the need for permanent loss of graft dysfunction and return to dialysis is warranted. The nature of bleeding risk as anticoagulation has to be restarted immediately after surgery in view of metallic prosthetic valve has to be explained
  5. IV unfractionated heparin has to be started after 6 hours of surgery and continued twice or thrice a day. Daily monitoring of coagulation parameters is warranted as post operative bleeding from the wound site and the drain site maybe an issue. After 4 days of surgery, warfarin has to be restarted at a low dose and PT INR is monitored to escalate the dose.
  6. Patient should receive stress dose of IV steroids as increased dose of steroids are required in those with suppressed HPA axis.
  • If the patient develops sepsis, I would only continue her stress dose of steroids and stop further immunosuppression. Infact, I would wait in the post operative period to start AZA till she is stable or about to be discharged as the benefit of immunosuppression outweighs the risk associated with it.

References:
Scotti A, Santangelo M, Federico S, et al. Complicated Diverticulitis in Kidney Transplanted Patients: Analysis of 717 Cases. Transplant Proc 2014;46:2247-2250.

Rehab Fahmy
Rehab Fahmy
3 years ago

How do you manage this lady?
1-Anticoagulation :transfer warfarin to heparin infusion.
2-Immunosuppression:glucocorticoids (transfer maintainace dose to hydrocortisone stress dose,stop azathioprine
3-good coverage with broad spectrum antibiotics
4-wound healing :care of wound and care against development of wound Collection
5-care of Preoperative CKD:good hydration ,avoid NEPHRO toxic drugs ,avoid hypotension and hypoperfusion , avoid electrolyte disturbance.

Post-operatively, she developed sepsis, how do you manage her immunosuppression
Stop azathioprine
Continue oh hydrocortisone stress doseasl
Good coverage with broad spectrum antibiotics
Care of sepsis : ً. Airway ,breathing ,circulation ,septic screen and good antibiotic coverage

Ben Lomatayo
Ben Lomatayo
3 years ago
  1. Counselling about the diagnosis & the surgical procedure
  2. Concern for the procedure
  3. History& physical examination including graft examination
  4. Pain control
  5. Basic blood and electrolytes including potassium & urine analysis
  6. Surgical review
  7. Anaesthetic review
  8. Volume status & electrolytes and acid base
  9. Cardiology review and consideration of unfractionated heparin postoperative
  10. Consideration of INR < 1.5 with cardiology approval( Vitamin K plus FFP)
  11. Post-operative Monitoring of UEs & electrolytes
  • in case of sepsis , we can give her stress dose steroids( increase the dose to 30 mg max if on prednisone 5mg) and reduction of antiproliferative dose to 50 mg azathioprine.
Nadia Ibrahim
Nadia Ibrahim
3 years ago

This lady is old age , mostly with chronic transplant glomerulopathy , CKD , most probably stage 3b or 4 , on oral anticoagulation with high INR beyond target non symotomatising but at high riskof bleeding, had an emergency perforated colon with risk for infection, on immune suppression and steroids
1)   Full lab evaluation, CBC, LFT, Bleeding profile ,, s.albumin and s.electrolytes, ABG
2)   Handling oral anticoagulation: stop warfarin ( 5 days prior to surgery if possible), shift to LMWH then stop one day before surgery, resume 24hours postop for bridging together with warfarin, and stop LMWH after 3 days
3)   Handling steroids: stop oral and shift to sress dose hydrocortisone of 100mg?8hs then resume oral 48 hours postop
4)   Stop azathioprine: Rationale: patient is already considered CKD stage 3b or 4, with high risk for infection , yet she should be informed with the decision and oriented with the sequences,
5)   Handling infection: good coverage with broad spectrum antibiotics
6)   Prepare emergency Bl units for Tx , FFP, vit K, hemostatics
 

  • Post-operatively, she developed sepsis, how do you manage her immunosuppression?
  • Stop azathioprine
  • Continue steroids stress dose
Dalia Ali
Dalia Ali
3 years ago

Management of lady

●Urgent – For those requiring urgent (eg, same day) reversal, we suggest administration of a 4-factor PCC with vitamin K

For patients who can wait 24 hours before going to surgery, vitamin K (dose 1 to 2 mg) will typically be sufficient to lower the INR; in such cases, PCC and FFP can be avoided. This calculation regarding the urgency of the required procedure should involve close consultation with the surgeon/interventionist.

●PCC – For patients with serious bleeding and INR >2, we suggest using a 4-factor prothrombin complex concentrate ((PCC))unactivated rather than a 3-factor PCC and/or Fresh Frozen Plasma (FFP) for rapid reversal, due to the similar efficacy and lower risk of adverse events with 4-factor PCC.

Management of sepsis

IMMEDIATE EVALUATION AND MANAGEMENT

Securing the airway (if indicated) and correcting hypoxemia, and establishing venous access for the early administration of fluids and antibiotics are priorities in the management of patients with sepsis and septic shock

Stabilize respiration — Supplemental oxygen should be supplied to all patients with sepsis, who have indications for oxygenation, and oxygenation should be monitored continuously with pulse oximetry.

Establish venous access — Venous access should be established as soon as possible in patients with suspected sepsis. While peripheral venous access may be sufficient in some patients, particularly for initial resuscitation, the majority will
require central venous access at some point during their course.

Initial investigations — An initial brief history and examination, as well as laboratory, microbiologic (including blood cultures)

●Complete blood counts with differential, chemistries, liver function tests, and coagulation studies including D-dimer level.

●Serum lactate – An elevated serum lactate (eg, >2 mmol/L or greater than the laboratory upper limit of normal) may indicate the severity of sepsis and is used to follow the therapeutic response

●Peripheral blood cultures (aerobic and anaerobic cultures from at least two different sites), urinalysis, and microbiologic cultures from suspected sources (eg, sputum, urine, intravascular catheter, wound or surgical site, body fluids) from readily accessible sites.

●Arterial blood gas (ABG) analysis – ABGs may reveal acidosis, hypoxemia, or hypercapnia.
●Imaging targeted at the suspected site of infection is warranted (eg, chest radiography, computed tomography of chest and/or abdomen).

●Procalcitonin

INITIAL RESUSCITATIVE THERAPY

●Tissue perfusion

Treating metabolic acidosis

Empiric antibiotic therapy

MONITOR RESPONSE

PATIENTS WHO FAIL INITIAL THERAPY

Vasopressors — Intravenous vasopressors are useful in patients who remain hypotensive despite adequate fluid resuscitation or who develop cardiogenic pulmonary edema. Based upon meta-analyses of small randomized trials and observational studies, a paradigm shift in practice has occurred such that most experts prefer to avoid dopamine in this population and favor norepinephrine as the first-choice agent

Reference

Up to date 2021

Mohamed Essmat
Mohamed Essmat
3 years ago

Management of the lady:
This is a surgical emergency, vital signs, full blood count, liver functions, kidney functions, serum bicarbonate level, sepsis parameters labs and ECG .
Fluid resuscitation , Warfarin should be stopped, fresh frozen plasma should be given to correct INR, if blood is needed it should be filtered and washed . She should continueon unfractionated heparin after the surgery according to the bleeding status if no complications , it usually starts 12 to 24 hrs after the surgery. Perioperative parentral antibiotics, IV hydrocortisone – 100mg/8hours for two days then decreased to 50mg/8hours for two days then continue on oral prednisolone .
If she developed sepsis post operatively :
Continue on hydrocortisone 100mg/8hours
temporary withdrawal of immunosuppression .Swab culture from the wound , blood culture , upgrading antibiotics .

Ramy Elshahat
Ramy Elshahat
3 years ago

How do you manage this lady?
This lady 73y with advanced ckd, metallic valve on warfarin, transplanted since 19 y and as a complications of steroids she suffered from perforated diverticulitis
We have multiple aspects here
High risk of bleeding regarding urgent major operation also her advanced ckd.
High risk of thrombosis regarding her metallic valve
High risk of infection regarding perforated GIT
So
1/1st blood culture should be obtained then antibiotics should be started immediately most common organisms gram -ve like enterococcus and anaerobic so 3rd generation cephalosporin or ciprofloxacin can be used although i would prefer to use meropenam as broad spectrum coverage in such fragile old lady
2,3/ risk of bleeding INR and thrombosis correction targeting INR below 1.5 using fresh frozen plasma then use of unfractionated heparine as abridge therapeutic targeting aptt triple Normal and to be stopped 4-6 h preoperative after cardiology consultantation
Postoperative heparine reintroduce according to hemostasis as soon as possible
And restart warfarin after 2days
4/regarding immunosuppressant medications :Continue azathioprine and give stress dose steroids 100mg hydrocortisone/8 and recontinue oral Prednisone after 2 days postoperative
5/regarding metallic valve: follow up echo heart and its better to fo trans esophageal echo if the patient developed fever or blood culture are positive.
Post-operatively, she developed sepsis, how do you manage her immunosuppression?
In case of life threatening sepsis it’s better to stop azathioprine after discussing with the patient or relatives of risking of losing the graft but saving the patient
In case of moderate infection its wise to half dose of azathioprine until improvement of sepsis for duration not exceeding 4w
If kidney function was better than this this patient will get benefits from shifting from antimetabolites to CNI tacrolimus

Akram Abdullah
Akram Abdullah
3 years ago

Optimize her condition by the following:
1- cardiac consultation, stop warfarin, keep INR between 1.5-2 perioperative , she might need FFP during the procedure & start therapeutic heparin infusion till day 5 with overlapping with warfarin.
2-Good coverage of antibiotics.
3- Good hydration avoid nephrotoxic medications
4-stop azathioprine,
5- monitoring of renal function test, she might need a temporary dialysis line.
postoperative immunosuppression if sepsis devloped, stop azathioprine, continue on steroid,

Tahani Hadi
Tahani Hadi
3 years ago

For this old age lady with History of renal transplantation 19 years ago and prosthetic valve on warfarin she needs to switch of warfarin to low molecular weight heparin 4-5 days before operation and keep her on LMWH till 12 hrs before operation and for those patients with higher risk unftactionated heparin should be used instead of LMWH and continue on it till 6 hrs prior to the operation, the target INR pre-OP.should be less than 1.5.
LMWH must be restarted 6-12hrs after the op. When the pt. is haemodynamicaly stable .
For this pt. I will keep her on the same IS with prophylaxis antibiotics .
If she developed sepsis post operative I will send her for Blood and urine culture , abdominal ultrasound, CBC, inflammatory markers and started with imperical antibiotics, stop azathioprine and low dose of steroid .
Reference
NCBI.(2013,November 4) .Anti coagulation for prosthetic valves. http://www.ncbi.nlm.nih.gov.
Medscape

Wael Hassan
Wael Hassan
3 years ago

1- stop warferin
-stop azathioprin
-increase dose of cortisol ( give solucortive 100mg TID)
-can use vitamin k and prepare FFP if needed
-high risk concent ,high risk of graft lose
-broad spectrum AB
2-give cortico steroid in higher dose , still stop azathioprine , start low dose CNI

Nazik Mahmoud
Nazik Mahmoud
3 years ago

How do you manage this lady?
Change warfarin to heparin till the operation ended and reintroduced after 3days
Post-operatively, she developed sepsis, how do you manage her immunosuppression?
If she developed sepsis I will discontinue azathioprine till she recovered

Dalia Eltahir
Dalia Eltahir
3 years ago
  • How do you manage this lady?

1st  we must discuss with patient about risk of graft loss .   
Warfarin should be stopped, fresh frozen plasma to correct INR as the patient has high risk of bleeding .She had mechanical valve we should continue by unfractionated heparin .fluid resuscitation .
Azathioprine should be discontinued as in presence of diverticulitis,
IV hydrocortisone – 100mg/8hours for two days then decreased to 50mg/8hours for two days then resume oral steroids
Post-operatively, she developed sepsis, how do you manage her immunosuppression
 Continue on hydrocortisone 100mg/8hours
temporary withdrawal of immunosuppression .Then we can control sepsis with broad spectrum antibiotics .
 
 



 

Nasrin Esfandiar
Nasrin Esfandiar
3 years ago

·       Q1: She is a high risk patient with chronic allograft nephropathy. We should stop warfarin before surgery and administer unfractionated heparin because it has short half-time and can monitor easily.
Hydrocortisone 100 mg IV Q8h (started before surgery) is indicated.
Then it is tapered to usual steroid dose before surgery after several days.
·      Q2: I will stop azathioprine and continue with stress dose steroids.
 

Mujtaba Zuhair
Mujtaba Zuhair
3 years ago
  • How do you manage this lady?

This patient needs urgent surgery , the INR is 3.5 so she needs to stop warfarin and administering FFP to correct her INR before surgery , we need bridging with unfractionated heparin after surgery after hemostasis is secured. Stress dose of IV steroids is needed in the perioperative period.

  • Post-operatively, she developed sepsis, how do you manage her immunosuppression?

If the patient developed sepsis , azathioprine should be stopped and continue on steroids to allow the body to response to the sepsis and after recovery from sepsis we can reintroduce azathioprine.

MOHAMMED GAFAR medi913911@gmail.com
MOHAMMED GAFAR medi913911@gmail.com
3 years ago

How do you manage this lady?

A-regarding her blood thinning medication pre op

i will dc warfrin pre op and i will shift her to LMWH sc bid prohylactic dose and to be stopped 12 hours befor or and counselling should be done regadring her risk of developing thrombotic event during or time .

B-regarding her immunsuppresion pre op
no need to change her immunsuprresion ,which is not explained to be only on streiods and antimetabilites only regardless she is now failing graft.

Post-operatively, she developed sepsis, how do you manage her immunosuppression?

1-rotuine blood tests in the form of full septic screen
2-routine fbc, full chmitsrey panel , esr, crp, pct,cmv pcr
3-to start guns of antibitiotc covering gram positive and gram negative and aneraboes
4-i will not change her immunosuppresion until she is severly ill with buliding up lactic acid regardless the antibiotics she is reciveing as she is already on very minimal immunsosuppresion

reffernce

Intensive Care Med (2019) 45:573–591 https://doi.org/10.1007/s00134-019-05597-y

Esmat MD
Esmat MD
3 years ago

1. Warfarin should be held due to imminent surgery and unfractionated heparin should be started in the setting of patient’s kidney dysfunction (possibly due to chronic allograft nephropathy) and the possibility of monitoring of the anticoagulant effect of UF-heparin and its short half-life.

Renal atheroemboli can also be considered as a differential diagnosis of her kidney dysfunction.

For major surgical stress, 100 mg of intravenous hydrocortisone should be given before induction of anesthesia followed by 50 mg every eight hours for 24 hours. Thereafter, the dose should be tapered down by half per day to maintenance level.

Delaying surgery to perform evaluation of the HPA axis would be inappropriate in this setting.

If the surgery is uncomplicated, the patient can continue azathioprine but, in this setting, a patient with diverticular perforation and at high risk of infection azathioprine should be discontinued.

2. In patients with life threatening infections or evidence of sepsis, all immunosuppressive agents should be withheld except for low-dose glucocorticoids. Antimetabolite should be discontinued indefinitely. So, in this patient, azathioprine should be discontinued.

 

 

Ahmed Omran
Ahmed Omran
3 years ago

1-Evaluation of hemodynamic stability and resuscitation if needed according to lab results. Preparation of suitable central line ,NGT ,and suitable blood components. Hydrocortisone in stress dosing and broad spectrum antibiotic prophylaxis.Shifting of warfarin to LMWH.
2-In case of postoperative sepsis ,azathioprine is stopped with use of broad spectrum antimicrobial coverage.

Ahmed Omran
Ahmed Omran
Reply to  Ahmed Omran
3 years ago

References
Kalil AC, Opal SM. Sepsis in the severely immunocompromised patient. Current infectious disease reports. 2015 Jun 1;17(6):3

Mahmud Islam
Mahmud Islam
3 years ago

In this emergent case, I guess the reason for acute renal failure (presumed) as she is 19 years transplant patient in the era of azathioprine, cyclosporin as many patients are still going well with such regimen are still monitored without shifting to newer drugs. here the issue is sepsis and we should stop azathioprine (https://www.ukcpa-periophandbook.co.uk/medicine-monographs/azathioprine). but apart from that in addition to supportive treatment supposing this patient is a low-risk patient I will try monitoring kidney function and urine output while os steroids alone as we did for many patients in the era of covid when needed. Here patient’s life is the primary concern followed by saving kidneys. as tacrolimus is nephrotoxic etc I will prefer balancing the risks and go with steroids (here wound healing and sugar etc can be taken under control and steroid may be tapered when the healing process could be foreseen

Shereen Yousef
Shereen Yousef
3 years ago

▪︎How do you manage this lady?
This lady has high basal s cr
She also has metallic valve
Her INR is 3.5
When complicated acute colonic diverticulitis occurs in transplanted patients, surgical intervention should be performed as soon as possible from the decision to operate
Emergency surgery for acute left side colonic diverticulitis is associated with higher mortality and morbidity in immunocompromised patients.
Mortality is influenced by the timing of intervention with patients operated on < 24 h from symptoms beginning showing better outcomes

Hartmann procedure is effective and safe in severely sick

half of all perforations happened within the first year after KT, when immunosuppressant drug doses are higher.

▪︎Mangment of immunosuppression
•steroids;
-In patients currently on steroid therapy or that have been in steroid therapy for the last year, there is no evidence regarding the necessity of the administration of a push-dose steroid in the event of a surgical intervention .

-No sufficient data exist to suggest the suspension of steroid medication before emergency surgery. Patients on steroids should remain on their usual regimen, 

-In the event of an inexplicable and fluid unresponsive hypotensive event immediately prior/after/during surgery, adrenal insufficiency should be part of the differential diagnosis and an i.v. push dose of 100 mg hydrocortisone should be administered.

-Perioperative stress steroid dose, however, is frequently used by anesthesiologists to reduce and prevent such dramatic effects in the postoperative period.
The most followed practical recommendation is to administer 200 to 300 mg of hydrocortisone during surgery. Evidence supporting this practice is insufficient .

-Stop Azathioprine if sepsis occures .

– ICU with close montion of CBC ,CRP, Blood pressure; temperature,fluid balance
Blood culture and wound swab .
-Avoid nephrotoxic drugs monitor doses according to e GFR .

-Antibiotic for Gram negative bacteria mainly ciftazidim and metronidazole to be adjusted according to culture.
-stop warfarin as her InR is high give unfractionated  heparin monitor with PTT
Resume warfarin 2 days after operation if no bleeding keep INR around 1.5.
– Give fresh frozen plasme to correct INR befor surgery.

Reference

Federico Coccolini, Mario Improta, …Fausto Catena.Acute abdomen in the immunocompromised patient: WSES, SIS-E, WSIS, AAST, and GAIS guidelines.World Journal of Emergency Surgery volume 16, Article number: 40 (2021).

Last edited 3 years ago by Shereen Yousef
Doaa Elwasly
Doaa Elwasly
3 years ago

-Azathioprine was reported to cause diverticulitis and bowel perforation particularly if used with high steroid doses for long periods as corticosteroid use was been described as a cause of spontaneous diverticular perforation .
So regarding managing this complicated case
-she needs to stop her warfarin  as her INR is 3.5 with high risk of surgical bleeding substituted by  unfractionated  heparin and to monitor PTT and since it is an urgent surgical case FFP can be given
– azathioprine dose can be reduced as well as oral steroids which can be sunbstituted with IV hydrocortisone  
-I f she developed sepsis postoperatively she needs to be manged in ICU under intensive care team care with nephrology and the surgical team, pan cultures need to be collected with aggressive Broad spectrum antibiotic treatment as she is immunocomprosmised  and this is  life saving  which is more crucial than graft saving as well as resuscitation with intravenous fluids and vasoactive drugs when needed and azathioprine can be stopped and oral steroids replaced by iv hydrocortisone .
This case being 73 y old  with her comorbidities having Mitral valve replacement with creat 325 umol/l on immunosuppressive therapy complicated with diverticular perforation and sepsis has a very poor prognosis
Reference
Bafi etal. Sepsis in Solid-Organ Transplant Patients. January 2017 – Volume 47 – Issue 1S – p 12-16.

Abdulrahman Ishag
Abdulrahman Ishag
3 years ago

 
How do you mange this lady ?

Perforation, is a complication of colonic diverticulosis commonly associated with autosomal dominant polycystic kidney disease (ADPKD), can be life-threatening in allogeneic kidney transplant recipients in the postoperative period. Immunosuppressive medications not only place the patient at risk for intestinal perforation, but also mask classic clinical symptoms and signs of acute abdomen, and subsequently lead to delayed diagnosis and treatment.

Management ;

A timely surgery can significantly reduce mortality. In cases of elective surgery, mortality and morbidity are similar to those of immune competent patients,
 
early surgery, with Hartmann’s procedure being, in our opinion, the best choice.

Before transplantation, elective surgery for colonic resection should be considered in patients with ADPKD or with a history of 1 or more episodes of acute diverticulitis who then regressed with medical therapy.

Pre operative ;
-ensure well hydration
– avoid nephrotoxic drugs
– minimize immune suppressant (decrease 50% of azathioprine dose )
– stress dose steroids
– this patient needs correction of coagulopathy ,using FFP
Intra operative ;
Ensure well hydration .
Record any hyotensive episodes   
 
Post-operativly ,she developed sepsis ,how do you mange her immunosuppressant ?

Sepsis in such patient is very difficult to deal with because;
– The immune suppressed state can modify the cardinal signs of inflammation, making accurate and rapid diagnosis of infection and sepsis difficult.
-antibiotic resistance has become a real issue.
–  increased risk for  rejection
 
Patient should be informed with these risks
 with hold anti proliferative Azathioprine
use stress dose steroid
Antibiotic therapy plays an important role in the management of complicated acute diverticulitis.

 
Reference ;
Biondo S, Trenti L, Elvira J, Golda T, Kreisler E. Outcomes of colonic diverticulitis according to the reason of immunosuppression. Am J Surg. 2016;21:384–90.
Scotti A, Santangelo M, Federico S, et al. Complicated diverticulitis in kidney transplanted patients: analysis of 717 cases. Transplant Proc. 2014;46:2247–50.
Chapman J, Davies M, Wolff B, et al. Complicated diverticulitis: Is it time to rethink the rules? Arch Surg. 2005;242:576–58
16. Von Rahden BH, Kircher S, Thiery S, et al. Association of steroid use with complicated sigmoid diverticulitis: potential role of activated CD68+/CD163+ macrophages. Langenbecks Arch Surg. 2011;396:759–68.
 
Kalil AC, Opal SM. Sepsis in the severely immunocompromised patient. Current infectious disease reports. 2015 Jun 1;17(6):32
 
 

Hamdy Hegazy
Hamdy Hegazy
3 years ago
  • How do you manage this lady?
  • Post-operatively, she developed sepsis, how do you manage her immunosuppression?

In this current scenario for
1-73-year-old lady.
2- 19 year old renal graft maintained on steroids and Azathioprine 100mg od. Current Cr 352 umol/L, e-GFR 11ml/min/m2 by MDRD, AKI/CKD.
3- Metallic Mitral valve on warfarin, INR 3.5.
4- Presented with acute abdomen and perforated sigmoid colon, planned for Hartman’s procedure.
Very high risk of mortality and morbidity scenario should be addressed with the patient and her family and next of kin (Death, Sepsis, Septic shock, Bleeding, Heart failure, valve dysfunction, renal failure, loss of the graft.
She should be managed in ITU setting, close monitoring environment, maintain stable hemodynamics.
Pre-operative preparation: routine investigations, group and save etc.
High INR: Stop warfarin, Use FFP to reverse it, not Vit K because vit K may be associated with warfarin resistance later when it is restarted post-operatively. Aim INR 1.5 for the procedure.
Uses unfractionated heparin UFH infusion and keep a-PTT in therapeutic range.
Warfarin should be restarted on day 2 post-operative as long as thereis no active bleeding, Keep UFH heparin, till INR reaches target level.
Antibiotic prophylaxis: mainly to cover G- negative bacteria and anaerobes (like ceftazidime and metronidazole).
Pan-culture to be sent.
Steroids: IV hydrocortisone 100mg tds on day 1, then 50mg tds till oral intake is initiated then oral prednisolone can be started.
Stop Azathioprine as long as there is evidence of sepsis which should be monitored clinically (fever, rigors, hypotension, infected discharges), high inflammatory markers (low or high WBC,CRP, procalcitonin), and positive cultures (blood, urine, discharge, wound swab, sputum).

References:
1/ Scotti A, Santangelo M, Federico S, et al. Complicated Diverticulitis in Kidney Transplanted Patients: Analysis of 717 Cases. Transplant Proc 2014;46:2247-2250.
2/ Bafi A., Tomotani D., and Rezende de Freitas F. Sepsis in Solis-Organ Transplant Patients.Shock. 2017;47(1):12-16.
3/ Tinist J., Sonneville R., Kalil A., et al. Diagnostic and therapeutic approach to infectious diseases in solid organ transplant recipients. Intensive Care Med, 2019;45:573-591.

Nandita Sugumar
Nandita Sugumar
3 years ago

Management 

Perforation of the intestine with INR increased is seen in this patient.

CBC, CRP, electrolytes, RFT, blood culture needs to be done. 

IV fluids need to be given. Give FFP since INR is increased. INR level of 1-1.5 needs to be achieved.  Warfarin should be stopped prior to surgery 24 hours before. It can be restarted after INR levels are stabilized post surgery. 

Azathioprine dosage titration should be done such that dosage is decreased. 

IV antibiotics as prophylaxis until blood culture results are confirmed.

Immunosuppression post op in case of sepsis : 

In case patient is seen to develop signs and symptoms of sepsis, then azathioprine is to be stopped. Sepsis is seen to be fatal in most cases and immediate action is required to prevent mortality. Injection hydrocortisone can be given to the patient after cessation of azathioprine. 

Antibiotics like ceftazidime , metronidazole can be given as dual antibiotic therapy according to the blood culture results. 

References : 

Jaffer U, Moin T. Perforated sigmoid diverticular disease: a management protocol. JSLS. 2008 Apr-Jun;12(2):188-93. PMID: 18435896; PMCID: PMC3016182.

Emily A. Zurbuchen, Nathalie Sela, Alexander Maskin,
Transverse Colonic Perforation in Renal Transplant Recipients During the Early Postoperative Period: A Case Series,
Transplantation Proceedings,
Volume 53, Issue 3,
2021,
Pages 1070-1074,
ISSN 0041-1345,
https://doi.org/10.1016/j.transproceed.2021.01.019.

Demling RH, Salvatierra O Jr, Belzer FO. Intestinal necrosis and perforation after renal transplantation. Arch Surg. 1975 Mar;110(3):251-3. doi: 10.1001/archsurg.1975.01360090021004. PMID: 1090285.

Arthur J et al. Restoration of normal prothrombin time/international normalized ratio with fresh frozen plasma in hypercoagulable patients. Clinical and applied thrombosis/Hemostasis. 2016, Vol 22 (1) 85-91 

Hinda Hassan
Hinda Hassan
3 years ago

How do you manage this lady?  
 This lady is considered high risk for thrombo-embolic complications and she has low GFR  of 10
1-     Anticoagulant: Stop warfarin at least 5 days before surgery and measure INR daily till reach a safe value. If still high add 1 mg oral vit K. cover this period with unfractionated heparin or LMWH started 36-48 hours after the last dose of warfarin and typically is stopped 24 hours or more (high risk of bleeding in surgery) before the surgery. In this patient low GFR , it is better to decrease and/or withhold the  last dose of unfractionated heparin
After the operation, therapeutic dose LMWH is given after 24 hours if no bleeding, and the warfarin  can be resumed on  day 2 after exclusion of any post surgical bleeding . The heparin is stopped when 2 separate INR are within the target therapeutic range ( if she has a history of   reaction to LMWH, fondaparinux can be used instead but we need to consider its longer half-life )1
2-     Immunosuppressive therapy need to be reduced or withdrawn.
3-     Surgery : need to be early  within 48 hours of symptom onset. The recommended procedure is Hartmann’s colonic resection and temporary colostomy with subsequent recanalization. Immediate anastomosis or cleaning/drainage of the abdominal cavity, without resection of the perforated area is better to be avoided 2
4-     Steroid: as this surgery is considered moderate risk , daily dose plus hydrocortisone 50 mg iv before incision followed by 25 mg tds for 24 hr then the usual dose3

1-Ortel, T. L. (2012). Perioperative management of patients on chronic antithrombotic therapy. Blood, 120(24), 4699–4705. doi:10.1182/blood-2012-05-423228 
2-Scotti, A., Santangelo, M., Federico, S., Carrano, R., La Tessa, C., Carlomagno, N., … Renda, A. (2014). Complicated Diverticulitis in Kidney Transplanted Patients: Analysis of 717 Cases. Transplantation Proceedings, 46(7), 2247–2250. doi:10.1016/j.transproceed.2014.
3-Melanie M. Liu, Andrea B. Reidy, Siavosh Saatee, Charles D. Collard; Perioperative Steroid ManagementApproaches Based on Current EvidenceAnesthesiology 2017; 127:166–172

  • Post-operatively, she developed sepsis, how do you manage her immunosuppression?

1-       Empirical    broad antibiotic and antifungal therapy with care to avoid antibiotic- immunosuppressant interactions
2-      detection of the infectious agent  through cultures
3-     Consider  withdrawing immunosuppressive drugs  
4-     Hydrocortisone on stress dose
5-     IV fluids in form of crystalloids   
6-       vasopressors according to the  current guidelines( norepinephrine is the first choice )     
Timsit, J.-F., Sonneville, R., Kalil, A. C., Bassetti, M., Ferrer, R., Jaber, S., … Van Delden, C. (2019). Diagnostic and therapeutic approach to infectious diseases in solid organ transplant recipients. Intensive Care Medicine, 45(5), 573–591. doi:10.1007/s00134-019-05597-y 

Theepa Mariamutu
Theepa Mariamutu
3 years ago

How do you manage this lady?

Gastrointestinal perforations were the second most frequent cause of emergency abdominal surgery after solid organ transplantation. The 57.5 % of the cases described in the literature occurred in kidney-transplanted patients for polycystic kidney disease. The prevalence of complicated diverticulitis is about 1-4%.

Issues regarding current presentation

  1. Perforated diverticulum at sigmoid colon
  2. Acute kidney injury (assuming baseline creatinine is normal) due to haemodynamic instability or sepsis
  3. Prolonged INR due to sepsis /DIVC
  4. Metallic valve on warfarin

Diagnostic measures:

  1. Septic parameters: FBC, CRP, PCT, blood cultures for bacterial (aerobic and anaerobic) and fungus
  2. Haemodynamic parameters – ABG – for acidosis, Lactate, IVC measurement to evaluate fluid status
  3. DIVC – Fibrinogen degradation product (FDP)
  4. Evaluate other organs- Liver function test, Chest x ray – to evaluate cardiac size, ECG – to evaluate the heart rhythm, if possible bedside renal ultrasonography and renal doppler

Treatment / Management
Haemodynamic

  • to assess the blood pressure – if its low, to resuscitate with 30mls/kg fluid preferably balanced crystalloids such as lactated Ringer’s solution or Plasma-Lyte A (SMART trial, surviving sepsis campaign)
  • to reduce the lactate as low as possible below 4 , as shown by study (LACTATE trial)
  • If require inotropes-noradrenaline is shown better survival than others
  •  Maintain mean arterial pressure more than 65mmhg in normotensive patients and 80-85mmhg in hypertensive patients  
  • Initial antibiotics Therapy
  • Start empirical antibiotics which broad enough to cover all likely pathogens -sulperazone and metronidazole then tailored according to culture

Immunosuppressive therapy

  • Withhold anti-metabolites in severe septic patients
  •  Switch oral prednisolone to IV hydrocortisone -watch out for adrenal insufficiency symptoms in prolonged steroid usage
  • Watch out for immune reconstitution syndrome (IRS)

Anticoagulation

  • to transfuse FFP prior to surgery as patient’s INR is prolonged. Aim the INR around 1.5
  • If DIVC, cycle of DIVC regime should be given accordingly
  •  To start IVI heparin post operation and measure aPTT

Post-operatively, she developed sepsis, how do you manage her immunosuppression?
Treatment of Sepsis is priority for now. I will do the sepsis control measures as I said above.

I would stop her Azathioprine and continue IV steroids.

  1. Bafi A., Tomotani D., and Rezende de Freitas F. Sepsis in Solis-Organ Transplant Patients.Shock. 2017;47(1):12-16.
  2. Tinist J., Sonneville R., Kalil A., et al. Diagnostic and therapeutic approach to infectious diseases in solid organ transplant recipients. Intensive Care Med, 2019;45:573-591
Hemant Sharma
Hemant Sharma
Admin
Reply to  Theepa Mariamutu
3 years ago

I agree with FFP infusion completely for reversal of INR but what are your reasons not to give Vit K.

Theepa Mariamutu
Theepa Mariamutu
Reply to  Hemant Sharma
3 years ago

I would like to give FFP in this case:

  • I would like to achieve immediate reversal of INR to assist emergency operation before patient deteriorates
  • Vitamin although as efficacious as FFP but it require around 6 hours to act
  • In the setting of sepsis, I would like to think about DIVC, so FFP will be better choice.
Mahmud Islam
Mahmud Islam
Reply to  Hemant Sharma
3 years ago

as in this article along with AHA guidelines vitamin k is not advice because of hypercoagulable states. still, low dose can be used but as my friend said, vitamin k will take more time

If the operation is not that emergent, I may prefer LMW heparin plus low dose vitamin k; for this patient 10 mg may be enough

I prefer FFP most of the time but in such 73 patient even acute MI is a risk of FFP
In case the operation may be postponed I may prefer LMW (here risky, but could use classic heparin) the reason is because of low eGFR, and ı can reverse with protamine more efficiently in case of unexpected bleeding (during or post-operation)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312231/

Mahmoud Hamada
Mahmoud Hamada
3 years ago

This patient has large intestinal perforation with abnormal elevated INR.
management:
1- IV fluid resuscitation
2- hold warfarin and give FFP to control INR so that she be fit for surgery.
3- blood work up: CBC with deferential, blood c/s, procalcitonin.
4- decrease dose of azathioprine
5- Broad spectrum Iv antibiotic coverage till results of blood c/s are obtained.
6- continue on steroid alone.

Last edited 3 years ago by Mahmoud Hamada
Hemant Sharma
Hemant Sharma
Admin
Reply to  Mahmoud Hamada
3 years ago

Please answer the second question of the scenario.

Heba Wagdy
Heba Wagdy
3 years ago
  • How do you manage this lady?

Resuscitation with IV fluids to maintain hemodynamics
patient is on warfarin and INR is 3.5, warfarin should be stopped, fresh frozen plasma to correct INR as the patient has high risk of bleeding
also has high risk of thromboembolism (due to mechanical valve) so bridging anticoagulation with IV infusion of unfractionated heparin has to be considered 24 hours after surgery if adequate hemostasis was obtained intraoperatively then oral anticoagulation should be resumed.
Azathioprine should be discontinued as in presence of diverticulitis, immunosuppression should be decreased
IV hydrocortisone – 100mg/8hours for two days then decreased to 50mg/8hours for two days then resume same oral steroids
blood culture and culture from the abdominal collection
IV antibiotic third generation cephalosporine and metronidazole
then antibiotics should be adjusted according to results of cultures

  • Post-operatively, she developed sepsis, how do you manage her immunosuppression?

The patient should stop azathioprine and continue on hydrocortisone 100mg/8hours
temporary withdrawal of immunosuppression will improve immunological response and allow to control sepsis with the broad spectrum antibiotics

Heba Wagdy
Heba Wagdy
Reply to  Heba Wagdy
3 years ago

references:
Kalil AC, Opal SM. Sepsis in the severely immunocompromised patient. Current infectious disease reports. 2015 Jun 1;17(6):32.
Siddharthan RV, Gardner IH, Lu KC. Diverticulitis in the immunocompromised patient. In Seminars in Colon and Rectal Surgery 2019 Sep 1 (Vol. 30, No. 3, p. 100689). WB Saunders.

Hemant Sharma
Hemant Sharma
Admin
Reply to  Heba Wagdy
3 years ago

Good answer. Would you warn the patient that her graft might be at risk peri-op/post-op

Fatima AlTaher
Fatima AlTaher
3 years ago

This is a very high risk pt (old age, cardiac, graft dysfunction and need emergent surgery
1- for anticoagulant therapy follow bridging protocol with discontinuation of warfarin, give FFP to decrease INR to 1.5 and give LMWT Heparin
2-For IS
Steroid : IV hydrocortisone 100 mg /6-8 h
Azathioprine : unchanged
Joudisiuos volume status control
Close monitoring of valve functions with frequent trans thoracic Echo
1-   Management of Sepsis
·       ICU admition
·       General measures as NPO ,  
·       Volume status management
·       Continue stress dose hydrocortisone
·       Blood, urine, wound cultures and give embrical c ombination antibiotic coverage till obtain the cultures  result s ( metronidazole , levofloxacin )

         UpToDate : Shapiro R ., Kidney transplantation in adults: Nontransplant surgery in the kidney transplant recipient. Topic 7317 Version 22.0

Hemant Sharma
Hemant Sharma
Admin
Reply to  Fatima AlTaher
3 years ago

Please provide evidence is support of your statement to continue Azathioprine

Reem Younis
Reem Younis
3 years ago

-This is a 73-year-old lady with diverticular perforation of the sigmoid colon, chronic allograft dysfunction, and high INR.Plan of management:
1. stabilized vital signs.
2. Nill by mouth and intravenous fluid NG-tube.
3. intravenous antibiotics that cover gram-negative and anaerobic bacterias. (ampicillin and metronidazole).
4. CBC, RFT with electrolytes, stool and urine analysis, blood for cluture and sensitivity, and CRP.
5.Intake and output chart.
6. Discontinues warfarin and give vitamin K and FFB to reduce INR to 1.5 post-surgery continue with unfractionated heparin and followed with PTT until the patient improved and can take orally then restart warfarin and reach target INR(2-3).
7. Discontiue prednisolone and start hydrocortisone 100mg /8h until the patient improved and can take orally.
If the patient develops sepsis postoperatively, azathioprine should be stopped until sepsis is treated and continued with steroids. Prescribe antibiotics according to culture and sensitivity
Reference :
THAD WILKINS,  KATHERINE EMBRY, and RUTH GEORGE. Diagnosis and Management of Acute Diverticulitis.Am Fam Physician. 2013 May 1;87(9):612-620..

Hemant Sharma
Hemant Sharma
Admin
Reply to  Reem Younis
3 years ago

What risk will Vit K bring and why are most surgeons reluctant to give Vit K for INR management in patients with metallic heart valves

Reem Younis
Reem Younis
Reply to  Hemant Sharma
3 years ago

because Vitamin K administration in large dose more than 5mg can lead to warfarin resistance.

Mahmud Islam
Mahmud Islam
Reply to  Hemant Sharma
3 years ago

More hypercoagulable states may issue, so vascular thrombosis maybe the concern in the postoperative period (I think)

Amit Sharma
Amit Sharma
3 years ago
  • How do you manage this lady?

This is an elderly lady with a transplant kidney received 19 years back, having graft dysfunction, on anticoagulation due to a prosthetic mitral valve, now presenting with acute abdomen revealing diverticular perforation of sigmoid colon. So, the management of this patient has multiple aspects:

1) Immediate resuscitation: It involves stabilization of the patient.

a) Securing intravenous access

b) Intravenous fluid for hemodynamic stability. Keep the patient nil per orally.

2) Preparation for surgery: This is an emergency, needs to be done as early as possible to prevent complications. There is an increased risk of mortality if surgical intervention is not done timely within 48 hours of presentation of symptoms. (1)

a) Laboratory work-up: Send complete blood counts, blood cultures, blood group and cross match, PT/INR. Arrange blood products including whole blood and FFP.

b) Management regarding coagulation profile: Surgery cannot be performed at INR of 3.5. Due to the emergent condition, warfarin should be stopped and FFP should be transfused to bring the INR below 1.5. Post-operatively, give unfractionated heparin infusion and monitor aPTT to keep in therapeutic range. Restart warfarin on post-operative day 2, if no active bleeding and taper off heparin infusion once target INR achieved.

c) Prophylactic antibiotics: In view of high risk of infection, prophylactic antibodies covering gram negative, gram positive and anaerobic organisms should be given (meropenem or Ceftazidime plus metronidazole).

d) Immunosuppression: Give stress dose of steroids – Injection Hydrocortisone 100 mg intravenous 8 hourly for one day, then 50 mg 8 hourly for next day and then oral prednisolone form post-operative day 2, if orally allowed. Withhold azathioprine till orally allowed, usually restart from post-operative day 2.

3) Intraoperative management: Send cultures from peritoneal fluid/ collection. Handle tissue and skin incision site carefully as it would help in post-operative wound healing.

4) Post-operatively: Care of wound site, early removal of lines like foley catheter and central lines to decrease risk of infection. Management of antibiotics as per culture and sensitivity, anticoagulation and immunosuppression as mentioned above. Watch for symptoms and signs of sepsis including fever, leukocytosis, elevated CRP and procalcitonin. If sepsis suspected, try to find focus of sepsis (usually the abdomen is the cause, but may be some other source like UTI, pneumonia or endocarditis).

  • Post-operatively, she developed sepsis, how do you manage her immunosuppression?

If she develops sepsis post-operatively:

1) Immunosuppression: Sepsis will be most important cause of increased morbidity and mortality in this setting, hence it is important to reduce immunosuppression. Stop azathioprine, continue injection hydrocortisone 100 mg IV 8 hourly.

2) Investigations and examination: CBC, CRP, procalcitonin, blood culture, urine routine and urine culture, drain culture (if any), chest X ray, 2D ECHO. Ultrasound to look for any collection, may require CT abdomen. Examine wound site to look for any local cause of infection.

3) Empirical antibiotics: Meropenem or ceftazidime with metronidazole, change according to culture reports.

References:
1) Scotti A, Santangelo M, Federico S, et al. Complicated Diverticulitis in Kidney Transplanted Patients: Analysis of 717 Cases. Transplant Proc 2014;46:2247-2250.

 

Last edited 3 years ago by Amit Sharma
Ala Ali
Ala Ali
Admin
Reply to  Amit Sharma
3 years ago

Excellent plan and up to the point
Do you think we should cover Gram-positive bacteria and why?

Last edited 3 years ago by Ala Ali
Amit Sharma
Amit Sharma
Reply to  Ala Ali
3 years ago

Yes we should cover Gram positive bacteria. Although the commonest organisms involved in intra-abdominal infections are aerobic gram negative bacteria, Gram positive bacteria are also seen in a substantial number of cases, especially associated with colorectal perforations.

Reference:
de Ruiter J, Weel J, Manusama E, et al. The epidemiology of intra-abdominal flora in critically ill patients with secondary and tertiary abdominal sepsis. Infection. 2009;37:522–527.

Hemant Sharma
Hemant Sharma
Admin
Reply to  Amit Sharma
3 years ago

Excellent answer Amit, Just to add mechanical mitral valves are more prone to thrombosis and surely need bridge therapy as you mentioned but bioprosthetic aortic valves may not need bridge therapy. Bridge therapy can lead to post-op bleeding and patient should be warned about it. The bridge therapy needs to be renal adjusted and consultation about further graft deterioration should be done. Add on, I shall always do CT in bowel surgery rather than a US scan.

Amit Sharma
Amit Sharma
Reply to  Hemant Sharma
3 years ago

Thank you for these points for patient management.

Mohammed Sobair
Mohammed Sobair
3 years ago

NPO.

NGT.

Maintain normovalemia IVF.

Monitor Uop.

Sepsis bundle.

For corticosteroid:

Intravenous hydrocortisone 100mg every 8hr, till patient can resume oral intake.

 Providing stress ulcer prophylaxis.

Hold warfarin ,Vitamin k 5mg iv.

Monitor INR when less than 2 , a short-acting agent such as unfractionated heparin or

LMWH may be used as a “bridge”.

Antibiotic:

IV therapy with cefazolin, cefuroxime, or ceftriaxone, all plus metronidazole or

ampicillin/sulbactam .

Stop  the immunosuppressive agents . 

Reference:

Thomas L. Orte. Perioperative management of patients on chronic antithrombotic

therapy. Blood (2012) 120 (24): 4699–4705.

AHRQ Safety Program for Improving Antibiotic Use 4 – Acute Care.

Hemant Sharma
Hemant Sharma
Admin
Reply to  Mohammed Sobair
3 years ago

Why Vit K and not FFP. would your management change is mechanical prosthetic valve was aortic

Mahmud Islam
Mahmud Islam
Reply to  Hemant Sharma
3 years ago

I do not have written evidence but from practice and cardiologic consultations and resğones and discussions. I general the gradient of the aortic valve is less than mitral so warfarin may be stopped even more safely for a couple of days.. (I forgot to order once for 4 days). In general, in the case of the mitral valve, cardiologists advise against LMWH (but of course, we have some challenges that should be managed individually. an operation is not like dialysis father of course but even with INR of 2.5 to save life dialysis catheter was performed safely with caution and support of Ultrasound guidance (balancing benefit is important)

saja Mohammed
saja Mohammed
3 years ago

She need emergency surgical intervetion old lady with acute graft dysfunction ? or acute on top of chronic allograft dysfunction with underlying comorbid disease prosethetic valve and on anticoagulation with warfarin INR > 3.5
she need HDU admission with urgent assessmnet of hemodyamic stabililty secure central line good hydration,group and save with blood crossmatch and ICU bed backup with urgent cardiovascular risk factors stratification stop warfarin and give VITK to correct the coagulpopathy with post -operative anticogalation with iv heparin infusion and 6 houlry APPT target ( 65-80 )as she had metalic valve( balance the risk of thrombsis vs bleeding ) she need multidesciplanry teams follow up including cardiologist , nephrologist and heamtologist ,
stress dose of steriod to aviod adernal suppression which is more in ( azahioprine and steriod ) hydrocortisone stress dose of 50-100mg IV 8 hourly with PPI prophylxis and broad sepctrum AB prophylaxis ( risk of wound infection and Infective enocraditis ) gram negative , gram postive and anerobic cover with sets of cultures prior and pot operative monitring with FBC , CRP as she is at risk of infection
stop azathioprine and start on cyclosprine IV in first 48 hours with trough level monitroing azathioprine carry more risk of infection due to bone marrow supperssion
and if the post operative ciurse complicated by sepsis will stop all immunsuppression therapy and continue on stress dose of steriod only

Last edited 3 years ago by saja Mohammed
Ala Ali
Ala Ali
Admin
Reply to  saja Mohammed
3 years ago

Thank you, Dr. Saja
In such a patient with chronic allograft dysfunction, would you manage without CNI? What precaution should you consider with IV cyclosporine? Is it available at your unit?

saja Mohammed
saja Mohammed
Reply to  Ala Ali
3 years ago

yes we can still use CNI in chronic allogrft dysfunction , regarding the cyclosporine iv avialable and we used it in ICU setting when patine got intubuated for surgical or other medical illness the iv dose usually one third of the regular oral dose slow IV infusion

Last edited 3 years ago by saja Mohammed
Huda Al-Taee
Huda Al-Taee
3 years ago

How do you manage this lady?

  1. ensure hemodynamic stability as much as possible.
  2. stop warfarin and give FFP + Vitamin K.
  3. IV antibiotics to cover gram negative, and anaerobic bacteria.
  4. convert oral steroid to IV hydrocortisone
  5. cover the postoperative period with unfractionated heparin.

Post-operatively, she developed sepsis, how do you manage her immunosuppression?

Stop azathioprine and continue on steroid treatment, in this case, the aim is to save patient’s life as the graft is already lost ( eGFR= 15 ml/min/1.73m2 ).

References;

  1. UpTodate 2021
  2. Bafi A.T.,  Tomotani D.Y.V., de Freitas F.G.R.Sepsis in solid organ transplant patients. Shock.2017; Vol.47, supplement 1, pp.12-16.
Wessam Moustafa
Wessam Moustafa
3 years ago

The patient should be stabilized preparing for surgery
NPO
IV fluids to keep her hydrated
Prophylactic antibiotics covering gram negative organisms
Stress dose of steroids ,hydrocortisone 100mg every 8hours
Stop warfarin and to be shifted to LMWH

Postoperative sepsis
I would maintenance adequate hydration .
Start IV empirical antibiotics
Withdraw blood and other cultures
Stop azathioprine and maintenance her on hydrocortisone

Dawlat Belal
Dawlat Belal
Admin
Reply to  Wessam Moustafa
3 years ago

Try to justify your answers.

Jamila Elamouri
Jamila Elamouri
3 years ago

How do you manage this lady?
Patient 19 years post transplantation stage 5 CKD, MV prosthesis, INR 3.5 (warfarin)
Acute abdomen with perforation of diverticulum.
1st the vital signs
She need central line (after manage INR) or two large cannulas, NGT
CBC, U/E/C, CRP/ peritoneal fluid and blood culture and sensitivety/ blood group and crossmatch, prepare 2 units PRBCs
Vit K, FFP to decrease INR < 1.5 before she enters the OT. UFH used postoperatively after hemostasis achieved. Warfarine restart after patient stabilization  
IV fluid resuscitation.
IV hydrocortisone 100 mg 8 hrly decreased post operatively to half the dose till patient can take orally.
IV antibiotic prophyalaxis against aerobic and anaerobic (ceftrixone + metronidazole)
She can restart her azathioprine post-operative
Care of the surgical wound as these patients have delayed wound healing.   
Post-operatively, she developed sepsis, how do you manage her immunosuppression?
I will stop the azathioprine as she at high risk from the infection.

Dawlat Belal
Dawlat Belal
Admin
Reply to  Jamila Elamouri
3 years ago

welldone .very good plan.

Assafi Mohammed
Assafi Mohammed
3 years ago

How do you manage this lady?

  1. Stabilization of hydration status, nutritional status and electrolytes balance.
  2. The patient is at high risk of thrombotic tendency because of mechanical MVR, she is also at high risk for bleeding considering the GI surgery. Benefit-Risk Ratio of bleeding versus thrombotic tendency of mechanical valve have to be considered. The eGFR is below 15 ml/ml/1.73 m2
  • In this situation, it’s an emergency and surgical intervention may be urgent because of perforation and localized sepsis which may exacerbate.
  • I will hold Warfarin 5 days before surgery. In the day of surgery if INR is >1.5, I will give Vitamin K. I will restart Warfarin in the night of surgery if starting oral intake.
  • Being at high risk for thrombosis; I will start UFH or LMWH after D/C of Warfarin. UFH IVI, to be discontinued 4 to 6 hrs prior to surgery. LMWH (eg; Enoxaparin) adjusted to her eGFR, to be given once/day at 1mg/kgBwt and to be D/C 24 hrs prior to surgery.(1)

Post-operatively, she developed sepsis, how do you manage her immunosuppression?

  • Stabilization of the general condition to keep the patient well hydrated and no electrolytes deficiency.
  • Septic screening: culture and sensitivity for blood and body fluid at perforated site.
  • Empirical antibiotics covering Gm+ve and Gm-ve organisms before C&S results being at hands(eg:Ceftazidime+ Augmentin + Metronidazole or Piperacillin/Tazobactam + Metronidazole (+/- Vancomycin).
  • AZA can precipitate bone marrow suppression causing leucopenia and severe infection. According to degree of sepsis and WCC affection I will decide whether to D/C AZA or to minimize the dose.

Referrences

  1. Guideline: Management of Anticoagulant Medications in the Periprocedural and Surgical Settings;Froedtert and Medical College of Wisconsin.
Dawlat Belal
Dawlat Belal
Admin
Reply to  Assafi Mohammed
3 years ago

fine answer but:
your last choice has to be clear:
degree of sepsis! with GFR around 15

Weam Elnazer
Weam Elnazer
3 years ago

How do you manage this lady?
The patient will start IV fluid once she is NPO.
100 mg of hydrocortisone is given intravenously every eight hours perioperatively, and the dose is slowly reduced (but not the frequency) until the patient can be switched to his or her regular doses of oral medications. (some centres use one dose of hydrocortisone 100 mg on the day of the surgery, and shift the patient to his routine oral dose once he is able to take it orally). as steroids can delay wound healing.
-Routine antibiotic prophylaxis, either with a first-generation cephalosporin or, in the case of dental procedures, oral amoxicillin, is ordinarily sufficient in most cases. I will recommend adding metronidazole as a prophylactic for anaerobes.

  • Post-operatively, she developed sepsis, how do you manage her immunosuppression?

as the patient is advanced CKD(stage5), old age and more than 19 years post-transplantation.after calculation of risk and benefits:
I will keep him on corticosteroid alone. no need for azathioprine.

-Regarding the anticoagulants :

the patient should maintain on anticoagulant as he has a metallic valve.
I will discontinue warfarin 5 days before surgery and insure INR <1.5 at the time of operation. the patient should be admitted to receive iv unfractionated heparin once the INR subtherapeutic. stop 6 hours pretransplant and check APTT immediately preoperatively

or give sc LMW heparin(which I do not prefer in this patient ) as he advanced CKD and may be unpredictable effect and need to decrease by 50 %

Dawlat Belal
Dawlat Belal
Admin
Reply to  Weam Elnazer
3 years ago

If she develops sepsis then this is the serious threat your concern is mainly:
hemodynamic stability
with her age,impaired graft function IS she can easily proceed to septicemia so antibiotic plan has to be more clear.
yuor anticoagulation plan is fine.

Mohamed Fouad
Mohamed Fouad
3 years ago

How do you manage this lady?

The current scenario of renal transplant patient with chronic allograft nephropathy with metallic mitral valve on formal anticoagulation with perforated viscus:
1-Rescusictation and maintain stable hemodynamics and use of BP support if needed.
2-Switch oral steroids to IV steroids stress doses 100 mg hydrocortisone /8 hours or 50 mg /6 hours
3-Stop Azathioprine to avoid bone marrow depression and development of sepsis in already immunocompromised patient.
4-Switch oral warfarin to UFH with regular monitoring of PTT and keep in the target level.
5-Analgesia and pain management: Avoid Morphine and codeine as they are contraindicated in advanced kidney failure because of the toxic accumulation of active metabolites. Recommended fentanyl or methadone
6-Blood cultures and serial inflammatory markers as CRP, procalcitonin, lactate level
7-Imaging to define any abdominal collection as a source of sepsis
8-IV antibiotics coverage according blood culture and sensitivities.

Post-operatively, she developed sepsis, how do you manage her immunosuppression?

Depends on steroids as a main immunosuppression and stop other immunosuppression until control of sepsis.

Dawlat Belal
Dawlat Belal
Admin
Reply to  Mohamed Fouad
3 years ago

weldone sepsis is the main threat.

Ban Mezher
Ban Mezher
3 years ago

Acute left colonic diverticulitis is associated with high morbidity (51%) & mortality (23%) in immunocompromised patients. Incidence of acute diverticulitis in transplant recipients around 1-2% & GI perforation is the second most frequent cause emergency abdominal surgery after SOT . Complicated diverticulitis among SOT recipients need surgical intervention as soon as possible. Hartmann procedure is safe & effective in severe & emergency surgery among immunocompromised patients.
To manage this patient urgently we need to no the following:

  1. risk of bleeding
  2. risk of thrombosis
  3. need for anticoagulation bridging
  4. time of anticoagulation discontinuation

The bleeding risk is high 2-4% ( operation time >45 min), risk of thrombosis also high ( prosthetic heart valve), INR > 1.5 so immediate stopping of warfarin is needed with IV vitamin K 5mg with FFP to reverse INR to <1.4 with post operative bridging with UFH or LMWH at least after 6-12 hr & continue bridging till the patient can resume oral intake then restart warfarin. Also the patient need IV steroid ( hydrocortisone).
Sepsis is the first or second leading cause of mortality in SOT recipients. In sepsis empirical using of antibacterial & anti fungal is am emergency strategy & it depend on specific risk factor of sepsis & MDR. Drug interaction between antibiotic & anti fugal with IS agent should be considered.
There is a conflict on management strategy of IS drugs among septic patients. Some suggest stopping IS to fasten sepsis recovery, but the benefit of this approach is not proven with increasing risk of graft loss due to rejection. Others recommend to use lower dose of IS & increase steroid dose.

References:

  1. Uptodate
  2. Bafi A., Tomotani D., and Rezende de Freitas F. Sepsis in Solis-Organ Transplant Patients.Shock. 2017;47(1):12-16.
  3. Tinist J., Sonneville R., Kalil A., et al. Diagnostic and therapeutic approach to infectious diseases in solid organ transplant recipients. Intensive Care Med, 2019;45:573-591.
  4. Coccolini F., Improta M., Stella M., et al. Acute abdomen in the immunocompromised patients: WSES, SIS-E, ESIS, AAST, and GAIS guidelines. World Journal of Emergency Surgery, 2021;16:40.
  5. deAngelis N., Esposito F., Memeo R., et al. Emergency abdominal surgery after solid organ transplantation: a systemic review. World Journal of Emergency, 2016;11:43.
Dawlat Belal
Dawlat Belal
Admin
Reply to  Ban Mezher
3 years ago

Good answer
what is your decision if she was in your center concerning:
IS
SEPSIS control.

Ban Mezher
Ban Mezher
Reply to  Dawlat Belal
3 years ago

Thank you, I will use low dose of IS, & sepsis treatment with wide spectrum antibiotics to cover gram positive & negative with anaerobic coverage

Mohamad Habli
Mohamad Habli
3 years ago

How do you manage this lady?

Infections in kidney transplantation can be difficult to diagnose because the immunosuppression reduce clinical signs and symptoms. So this patient is at high risk to develop sepsis and severe sepsis. Especially in this case of intestinal perforation, infection which mixed aerobic and anaerobic flora is expected. It is known that steroids increase risk of diverticulitis and colonic perforation by diminishing mucosal immune surveillance.
In this case the most common pathogens are Enterobacteriaceae and anaerobes. The empirical antibiotic of choice, in this case, is third generation cephalosporin or B lactam with B lactamase inhibitor to be started before surgery. Blood culture is recommended as half of patient develop bacteremia which is associated with 10% increase in mortality. Especially in this case metallic mitral valve which increases the risk of endocarditis, with the risk of bacteremia aggressive antibiotics to cover gram negative and anaerobic bacteria should be done. Intraoperative culture is mandatory as it guides our best option and duration of treatment.
In regards to steroids, patients receiving steroids as a maintenance therapy should be maintained on a higher dose of steroids in the intravenous form, and should be started preoperatively as patients on chronic steroids are at higher risk of acute adrenal insufficiency caused by suppression of pituitary-adrenal axis due to surgery related stress.
Taking in consideration the high risk of bleeding with this advanced CKD and also the risk of mitral valve thrombosis, the decision to stop warfarin and start continuous heparin infusion with targeting therapeutic PTT. Warfarin can be resumed in 48 hours after the surgery if there is no ongoing bleeding.

Post-operatively, she developed sepsis, how do you manage her immunosuppression?

As well known that immunosuppression is associated with increase risk of infection as the immune protective elements are suppressed. If sepsis develops, then the worsening of sepsis to severe sepsis and septic shock is likely, so our approach to stop azathioprine. But the patient has advanced chronic kidney disease stage 5, and she may develop worsening of kidney function if antimetabolite is stopped. However the risk of infection consequences is more unfavorable in comparison to risk of rejection. Patient already has advanced CKD and she probably will progress to ESRD even without infection. So in this case, with development of sepsis, stopping immunosuppression is the right option.

Dawlat Belal
Dawlat Belal
Admin
Reply to  Mohamad Habli
3 years ago

Your decisions are very wise and well planned.
thankyou for mentioning the artificial valve (being metalic what is the possibilty of SBE maybe in the anulous so antibiotcs along with anticoagulants an eccho follow up)
welldone.

Sherif Yusuf
Sherif Yusuf
3 years ago

How do you manage this lady?

Immunosuppression

  • Switch to intravenous hydrocortisone on the day of operation in a dose of 100 mg every 8 hours and from day 1 the dose is reduced ( not frequency ) and the oral preoperative dose of prednisolone can be resumed on day-2 post-operative
  • Keep azathioprine dose the same and can be given PO post-operative once she can take oral

Antibiotic prophylaxis

  • Patients on immunosuppression are at high risk of post-operative infections
  • Giving 1 dose of prophylactic antibiotic within 2 hours before initial incision may decrease the risk of post-operative infection
  • No antibiotic prophylaxis is indicated to prevent infective endocarditis (1)
  • The preferred antibiotic, in this case, is antibiotics that cover enterococci such as ciprofloxacin

Wound healing

  • Wound healing is a problem in all immunosuppressed patients and the time required for healing is generally 3 times that needed for healing of a wound in non-immunosuppressed patients
  • Steroid use is associated with poor wound healing
  • Strategies to decrease the skin complications due to immunosuppression, include delicate handling of the tissues during operation and if skin staples are used they may be kept in place for triple the duration needed for non-immunosuppressed patient owing to delayed wound healing in these patients

Management of thrombotic and bleeding risk

  • Mitral valve replacement indicates that the patient is at high risk of thrombosis, renal impairment indicates that the patient is at high risk of bleeding
  • So it is recommended to stop warfarin 3-4 days before the operation, once INR is below the target bridging is indicated either by UFH infusion or LMWH
  • UFH should be stopped 4-6 hours before operation while enoxaparin should be stopped 24 hours before the operation
  • Once INR < 1.5 operations can be done
  • Warfarin is resumed 12- 24 hours after the operation
  • Heparin infusion or LMWH should be resumed 48 to 72 hours after the operation depending on hemostasis
  • Heparin can be stopped after resuming target INR

Post-operatively, she developed sepsis, how do you manage her immunosuppression?

  • In case of life-threatening infections, it is recommended to withhold all immunosuppressive medications except low-dose corticosteroids. So stop azathioprine indefinitely, tacrolimus can be started 1 week after resolution of infection according to risk assessment of the patient
  • In case of moderate infection requiring admission and IV antibiotics, antimetabolite should be withheld for 4 -6 weeks then restarted at half of the original dose; if infection recur again antimetabolite should be discontinued indefinably, tacrolimus can be started 1 week after resolution of infection according to risk assessment of the patient
  • In moderate to severe fungal infection consider decreasing corticosteroid dose

   

  • In a stable patient with an infection, no modification of immunosuppression is recommended and only treatment of infection is required

REFERENCES

1.      Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 2007; 116:1736.

Dawlat Belal
Dawlat Belal
Admin
Reply to  Sherif Yusuf
3 years ago

your anticoagulation plan is acceptable
Your SEPSIS planis missing Blood culture
culture of peritonitis fluid both for aerobes and anaerobes this should formulate choice of antibiotics.
She is 19 years post tx. creatinine is 352 ,the balance is between managing sepsis versus compromised graft function in this elderly patient.

Riham Marzouk
Riham Marzouk
3 years ago

management :
1- give methylprednisolone
2- follow up of bl.p and UOP.

if developed sepsis:
withdrawal of azathioprine and keep on steroid with close follow up , if sepsis profile improved, will add tacrolimus

Prakash Ghogale
Prakash Ghogale
Reply to  Riham Marzouk
3 years ago

How do you manage this lady?
cardiology consult
Stop warfarin
FFP
VIT K
Stop azathioprine
iv fluids once NBM
Stress dose of steroids in the peri operative period 100mg hydrocortisone 8 hrly ,decrease by 25% every day and shift onto equivalent dose of oral prednisolone.
Post op LMWH

Post-operatively, she developed sepsis, how do you manage her immunosuppression?
Azathioprine has already been stopped
Stress dose of steroids in the peri operative period 100mg hydrocortisone 8 hrly ,decrease by 25% every day and shift onto equivalent dose of oral prednisolone.

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