MEDICAL GRANDROUNDS Eduardo O Yambao Jr MD Objectives

MEDICAL GRANDROUNDS Eduardo O. Yambao Jr. , MD

Objectives • To discuss a case of hemolytic uremic syndrome (HUS) and bilateral renal cortical necrosis (BRCN) resulting from septic abortion. • To discuss the diagnosis and treatment for HUS and BRCN

J. J. • 34 y/o female • Single • CC: Hypogastric Pain

History of Present Illness • 2 days PTA • had an induced abortion done • Few hours after, mild hypogastric pain • No fever • Took analgesics (aspirin, naproxen, paracetamol) affording temporary relief

History of Present Illness • Few hours PTA • Severe hypogastric pain not relieved by pain meds • Vaginal bleeding • No fever • No weakness • Consult at OB • Advised immediate curettage and admitted

Review of Systems • General: no weight loss, no pallor, no fever • Chest: no dyspnea, no cough, no colds, no hemoptysis • Heart: no chest pain, no palpitations • GU: no dysuria, no hematuria, no oliguria • Extremities: no edema

Past Medical History • Non hypertensive, non diabetic • History of bronchial asthma – last attack 1 year ago • No known allergies

Obstetrical History • G 2 P 1 (1 -0 -1 -1) • LMP: October 25, 2008 • PMP: September 2008

Family History • • No hypertension No diabetes (+) bronchial asthma – both sides No cancer

Personal and Social History • Non-smoker • Occasional alcoholic beverage drinker • No illicit drug use

Physical Examination Alert, awake, conversant, in pain BP 100/70 HR 90 RR 19 afebrile Anicteric sclera, pink palpebral conjunctivae Thyroid gland not enlarged, no lymphadenopathy, neck veins not distended • No tonsillopharyngeal congestion, no lymphadenopathy • Equal chest expansion, no retractions, clear lungs • •

Physical Examination • Adynamic precordium, AB 5 th LICS MCL, no murmurs • Abdomen flabby, soft, (+) direct tenderness on hypogastric area, no guarding, no rebound tenderness, no hepatosplenomegaly • No CVA tenderness • No edema • No acrocyanosis • Pulses full and equal

Physical Examination • Speculum examination : placental tissue plugging the os with minimal bleeding • Internal examination : dilated cervix 1 cm all the way.

Assessment • G 2 P 1 (1011), Incomplete Abortion, Induced Abortion, t/c Septic Abortion

Course in the Ward

Day of Admission • • Kept on NPO Underwent stat completion curettage Cefazolin 1 gram IV single dose given D 5 MR 1 L x 8 hours with 10 units oxytocin

Day of Admission • • Post currettage Cefalexin 500 mg tab, 3 x/day Metronidazole 500 mg tab, 3 x/day Methylergometrine 125 microgram tab, 3 x/day for 3 days

Day of Admission BP 80 -90 / 60 Hooked to voluven 500 ml, fast drip Referred to infectious disease service Impression : septic shock secondary to pelvic inflammatory disease due to induced abortion • CBC, Blood culture • Discontinue cefalexin • •

Blood culture: enterococcus faecalis (grp D), sensitive to ampicillin, penicillin CBC Hgb 12. 9 Hct 37. 9 Wbc 28. 09 Mye 4 Meta 3 Stab 4 Seg 86 Lym 1 Plt 30 k

Day of Admission • Start ampiclllin-sulbactam 1. 5 gram IV every 12 hours • Amikacin 750 mg IV every 24 hours • BP 70/50 placed on trendelenburg • Fast drip 200 ml PNSS and regulate to 100 ml/hr

Course in the Ward • 0610 H – Referred to hematology – PT/PTT – Peripheral blood smear – Fibrinogen level – Hematology: facilitate platelet transfusion 6 units or 1 unit platelet apheresis and 6 units FFP – Impression : Suspect hemolytic crisis: t/c Hemolytic Uremic Syndrome

Peripheral blood smear : predominantly normocytic normochromic, spherocytes, no nucleated rbc’s, wbc adequate, thrombocytopenia Fibrinogen : 432. 30 mg/d. L Feb 18 PTT Patient 41. 9 Control 27. 4 PT Patient 17. 1 Act 53. 2 Control 11. 8 INR 1. 46

Course in the Ward • 1135 H – No urine output for 5 hours: – Refer to nephrology : Ischemic Acute Tubular Necrosis Secondary to Septic Shock – Stat ultrasound of the whole abdomen : Bilateral renal parenchymal disease, enlarged uterus with echogenic endometrium, minimal ascites Na 139 K 4. 2 Cl 103 Phos 3. 98 Mg - Calc 5. 91 BUN 37 CREA 4. 69 Uric A. 7. 17 ALT 57 AST 519 CHON 3. 7 Alb 1. 7 Glob 2

Course in the Ward • 1315 H – BP 70/50 HR 110 RR 24 JVP 12 -14 – Mottled skin, cold extremities – Post secalon line insertion left femoral – Discontinue voluven, start dopamine 400 mg in 250 cc. D 5 W x 8 ml/hr (10, cg/kg/hr); noradrenaline (levophed) 8 mg in 100 cc D 5 W x 10 cc/hr – Transfer to ICU

Course in the Ward • First Hosp Day 0820 H – CVP 16 cm. H 20 (+) fine rales both lower lung fields anuric, temp 39. 1 BP 80/40 o 2 sat 83% – Discontinue PNSS, portable CXR stat – Shift to MVM 50% – pulmo referral

Course in the Ward • CXR : pulmonary congestion , no effusion, no infiltrates

Course in the Ward • First Hosp Day 0915 H – O 2 sat 74%, patient is intubated – AC Fio 2 100% Vt 400 RR 20 – Impression of pulmo service : Acute Respiratory Failure probably secondary to fluid overload versus Acute Respiratory Distress Syndrome (ARDS) – triple lumen catheter insertion , right – Stat dialysis

Course in the Ward • First Hosp Day - Ampicillin-sulbactam discontinued - started with Piperacillin-Tazobactam 2. 25 grams IV every 8 hours - after dialysis : given Vancomycin 1 gram IV for 1 dose - CT scan of the abdomen

Course in the Ward CT scan of the Whole Abdomen – Prominent uterus, minimal fluid collection in the cul de sac – bilateral renal cortical necrosis, absence of contrast excretion may be due to severe hypovolemia or may be a sign of acute renal failure

Course in the Ward • Fourth Hosp Day - therapeutic plasma exchange - Piperacillin Tazobactam shifted to Meropenem 500 mg once a day and Levofloxacin 500 mg IV for 1 dose then 200 mg IV every 48 hours

Course in the Ward • Seventh Hosp Day - improvement in the platelet count and LDH levels (plt 413, 000 and LDH 646 from 2, 532) - still anuric - started on Hydrocortisone (Solucortef) 100 mg IV every 8 hours

Course in the Ward • Eighth Hosp Day - rpt CXR : clearing of pulmonary congestion, stable vital signs, good oxygen saturation - off inotropes ; extubated - NGT removed, started on soft diet • Ninth Hosp Day - perm cath was inserted - started on Epoetin 5000 IU 4 x/wk

Course in the Ward • Eleventh Hosp Day - transferred to a regular room • Twelfth Hosp Day - IV steroid shifted to Prednisone 5 mg, 1 tablet 2 x/day

Course in the Ward • Fifteenth Hosp Day - discharged - will undergo follow-up hemodialysis 3 x/wk as an out patient

Final Diagnosis • • • Septic Abortion Septic Shock Hemolytic Uremic Syndrome (HUS) Bilateral Renal Cortical Necrosis s/p completion curettage, s/p perm cath insertion, right IJ

Septic Abortion • Serious complications : 1. Severe hemorrhage 2. Sepsis 3. Acute renal failure

Hemolytic Uremic Syndrome (HUS) • Pentad : 1. hemolytic anemia 2. thrombocytopenia 3. neurological symptoms 4. renal involvement 5. fever

Two Forms of HUS • Diarrhea – associated HUS (D+HUS) • Non Shiga toxin – HUS (D-HUS)

Pathogenesis • Characteristic lesion in HUS is thrombotic microangiopathy • Hallmark of thrombotic microangiopathies : widespread “hyaline” thrombi in terminal arterioles and capillaries • Initiating mechanisms : endothelial injury and activation of intravascular thrombosis

Hyaline thrombi in the lumen of glomerular capillary loops (arrows).

Pathogenesis • Typical pathologic lesion 1. platelet aggregation of arterioles and capillaries out of proportion to fibrin deposition 2. endothelial damage 3. lack of inflammatory infiltrate 4. regional differences in microcirculatory involvement

Pathogenesis • Acute cortical or tubular necrosis may occur. • Immunofluorescence studies invariably demonstrate fibrinogen along the glomerular capillary walls and in arterial thrombi.

Pathogenesis • During pregnancy the kidney seems to be particularly susceptible to damage by mechanisms involving intravascular coagulation.

Pathogenesis • Evidence of renal involvement is present in the majority of patients with HUS • Microscopic hematuria (78%) are the most consistent findings • More than 90% of patients with HUS have significant renal failure, one third of whom are anuric

Acute Renal Failure in Pregnancy • Acute renal failure (ARF) in pregnancy bears a high risk of bilateral renal cortical necrosis (BRCN) and consequently of chronic renal failure

Renal Cortical Necrosis (RCN) • Rare cause of acute renal failure in developed countries • Still occurs in developing countries due to poor health facilities • Occurs in 2 peaks : 1. early infancy – severe perinatal events 2. women of childbearing age

Pathogenesis • Causes of RCN can be divided into two groups: Obstetric and non-obstetric • Obstetric complications : 1. abruptio placentae 2. septic abortion 3. eclamptic toxaemia 4. post-partum haemorrhage 5. intrauterine fetal demise

Renal Cortical Necrosis (RCN) • Due to poor health facilities, RCN is still a cause of morbidity and mortality in developing countries. The damage is permanent and functional loss is irreversible.

Renal Cortical Necrosis (RCN) • Septic abortion continued to be an important cause of RCN and endotoxin-mediated endothelial damage leads to vascular thrombosis and subsequent renal ischemia in patients with septic abortion

Clinical Manifestations • most common : 1. CNS changes 2. purpura or bleeding from other sites 3. malaise 4. abdominal pain 5. fever • CNS symptoms : mild confusion and headache to frank paresis, aphasia, paresthesias, visual problems, seizures, and coma

Clinical Manifestations • Additional clinical findings: 1. petechiae 2. icterus secondary to intravascular hemolysis 3. indirect hyperbilirubinemia 4. signs of involvement of other organs.

Diagnostic Tests • The microangiopathic hemolytic anemia of HUS is distinguished from that of DIC by the absence of gross deviations from normal in the prothrombin and partial thromboplastin times.

Diagnostics Tests • Definite diagnosis for BRCN : renal biopsy • CT scan : representative and specific imaging procedure of kidneys for BRCN • A very unstable hemodynamic status with coagulopathy in the early period of hospital was not suitable for the procedure of renal biopsy.

Treatment • Plasmapheresis may remove the recently identified inhibitory antibodies against v. WF protease from the circulation and supply larger amounts of the protease enzyme • Plasma exchange should be performed daily until remission is achieved, remission being normalization of platelet count, or resolution of neurologic symptoms, or both.

Treatment • Supportive measures : 1. dialysis 2. antihypertensive medications 3. blood transfusions 4. management of neurologic complications

Treatment • plasma exchange (plasma pheresis combined with fresh frozen plasma replacement) is currently the treatment of choice and is superior to plasma infusion alone

Treatment • Plasma exchange (PE) has been shown in several case series to produce response rates of approximately 80% and survival rates greater than 90%. • The most important determinant of long term survival is the presence or absence of a serious underlying medical condition.

Treatment • Severe renal insuffiency resulting from HUS often requires dialysis. • Renal transplantation has also been performed

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