Postpartum%20hemorrhage Treatment

Uterotonic Agents for Active Management of the 3rd Stage of Labor

• Prophylactic uterotonic agents should be offered to reduce the risk of postpartum hemorrhage (PPH) 
• Selection of uterotonic agents will be dependent on the availability of the drug, syringes and needles along with storage capabilities (Oxytocin and Ergometrine injectables require refrigeration)

Carbetocin

• A synthetic analogue of Oxytocin with longer duration of action
  • An alternative to Oxytocin if it is not available or if titrable intravenous (IV) infusion of Oxytocin is not possible
• Some studies show that Carbetocin is well tolerated and appears as effective as Oxytocin
• May be used as a 1st-line agent for prevention of uterine atony and PPH following cesarean section or vaginal delivery with 1 risk factor
• Decreases the need for uterine massage to prevent PPH after vaginal delivery

Carboprost

• A synthetic 15-methyl analogue of prostaglandin F_2α
• Effective agent for increasing uterine tone
• May be used for the treatment of PPH caused by uterine atony which is unresponsive to conventional management 
• Should not be used in women with cardiovascular (CV), pulmonary, renal or hepatic dysfunction

Ergometrine (Ergonovine)

• Ergot alkaloid that can produce intense, sustained contractions in the puerperal uterus
• Used in the prevention and treatment of PPH when Oxytocin is not available
• An alternative 1st-line drug in developing countries or limited-resource settings  
• Should not be used in women with hypertension, heart disease, preeclampsia, eclampsia, Raynaud’s phenomenon, or scleroderma or women on HIV protease inhibitors 

Methylergometrine (Methylergonovine)

• Used in the prevention and treatment of PPH when Oxytocin is not available
• Tetanic contractions of the uterus occur within 5 minutes of intramuscular (IM) injection
• Should not be used in women with hypertension, heart disease, preeclampsia, eclampsia, Raynaud’s phenomenon, or scleroderma

Misoprostol

• Synthetic analogue of prostaglandin E₁ that causes uterine contraction
• May be given as an alternative when Oxytocin is not available or cannot be safely used to prevent or treat PPH
• Oral or sublingual (SL) Misoprostol can be given as an adjunct to 1st-line agents for prophylaxis in patients at high risk for PPH and as an adjunct to 2nd-line uterotonics for treatment of all patients with active PPH
  • 600 mcg may be given orally to prevent PPH and 800 mcg SL to treat PPH
• Can be given to patients with asthma or hypertension
• Used during controlled cord traction only when a skilled attendant is present at the birth

Oxytocin

• Preferred agent for prevention of PPH for all births; it has a rapid onset (2-3 minutes) and it does not elevate BP or cause tetanic contractions
  • Women at low and high risk for PPH may be given prophylactic IM and IV Oxytocin, respectively
  • It is recommended that Oxytocin be administered within 1 minute of delivery of the baby
  • Consider giving a 2nd-line uterotonic if response is inadequate within 4 minutes of Oxytocin administration
• In settings where Oxytocin is unavailable, the use of other injectable uterotonics or oral Misoprostol is recommended for prevention of PPH
• A 1st-line therapeutic uterotonic, it is effective in treating uterine atony if PPH occurs
• Several studies have demonstrated that routine use of Oxytocin in the 3rd stage of labor can reduce the risk of PPH by more than 40%
• Oxytocin can be used in all women: Women delivering vaginally in the absence of risk factors for PPH and those delivering by cesarean section to stimulate uterine contraction and to reduce blood loss  

Oxytocin/Ergometrine

• Appears to be more effective than Oxytocin used alone and has been used in the prevention and treatment of PPH
  • Reduces the risk of minor PPH, ie 500-1000 mL 
• Associated with more side effects than Oxytocin alone and cannot be used in women with high BP, heart disease, preeclampsia, or eclampsia

Other Agent

Tranexamic Acid

• An antifibrinolytic, it may be used as an adjunct to 1st-line agents for prophylaxis in patients at very high risk for PPH and as an adjunct to 2nd-line uterotonics for treatment of all patients with active PPH
  
  • IV Tranexamic acid may be used with Oxytocin in women delivering by cesarean section who are at increased risk of PPH  
• Recommended to be given as soon as PPH is diagnosed within 3 hours of delivery 

• Resuscitative efforts should be initiated with changes in patient's vital signs and accurate measurements of continuing blood loss
• Institute ABCs of resuscitation: Assess airway and breathing and evaluate circulation

Massage the Uterus

• Palpation and rubbing of uterine fundus may stimulate uterine contraction

Oxygenation

• Establishment of airway is the very first step in resuscitation
• Oxygen (O₂) by mask may be administered and endotracheal intubation may be necessary in the obtunded patient or those with impending respiratory fatigue
• A high concentration of oxygen at 10-15 L/min can be given to maintain oxygen saturation at ≥95% 

Fluid Resuscitation

• Until blood is available, begin fluid resuscitation with infusion of warmed clear fluids  
• Maintain 2 large IV lines; peripheral IV access using large-bore needle allows for a faster flow rate of IV fluids
• Target an SBP of 90 mmHg and urine output of >30 mL/hr

Crystalloid Solution

• Eg Ringer’s lactate, normal saline (NS)
• Crystalloid solutions are widely available, safe and inexpensive but they move rapidly from intravascular to extravascular space
  • ≥3x the volume of fluid lost will be needed as replacement and tissue edema ensues
• Initial crystalloid resuscitation of 1-2 mL for every 1 mL of blood loss may be done but should depend on patient's clinical condition and estimated blood loss 
• Ringer’s lactate may be preferred if large volume (>10 L) is required to avoid hyperchloremic acidosis associated with prolonged use of NS

Colloid Solution

• Eg albumin, hydroxyethyl starch, dextrans and gelatins
• Colloid solution contains osmotically-active molecules which stay in the intravascular compartment expanding its volume
• Use of these agents is limited by cost and availability and a meta-analysis has suggested that isotonic crystalloid solutions have better outcome when used for IV fluid resuscitation
• May be used together with crystalloids

There is no role for hypotonic dextrose solutions (D5W or diluted NS in 5% dextrose in water) in the management of hemorrhagic shock

Blood Transfusion

• Indicated when blood loss is >150 mL/min and patient is unresponsive to uterotonic therapy, when total blood loss is rapidly nearing the calculated maximum allowable blood loss, or when patient with hemoglobin <90 g/L develops tachycardia or shortness of breath that is unresponsive to fluid resuscitation
• Patients with blood losses of >20-25% and those with suspected coagulopathy require transfusion
• Packed red blood cells (RBCs) are used to restore intravascular volume and oxygen-carrying capacity of the blood
  • If immediate transfusion is needed, patient may be given emergency group O, rhesus D (RhD)-negative packed RBCs then switch to group-specific RBCs when feasible 
• Fresh frozen plasma (FFP) can be given when partial thromboplastin time (PTT) and prothrombin time (PT) are prolonged 
  • If no hemostatic test results are available, FFP can be infused after RBC transfusion if bleeding is ongoing or early FFP can be considered with delayed detection of PPH or for conditions such as placental abruption, abnormal placentation or amniotic fluid embolism 
• A 1:1 plasma to RBC transfusion ratio is advised, especially if bleeding is uncontrolled 
• Platelet concentrates are indicated if platelet count is <20,000-50,000/mm³ and hemorrhage is continuing
• Cryoprecipitate may be given for fibrinogen replacement with fibrinogen level <2 g/L

Avoid Hypothermia

• Measures to maintain euthermia include keeping the patient dry, warming all fluids to be used, utilizing warmed blankets or forced air warmers

Vasoactive Agents

• Inotropic and vasopressor agents (eg Phenylephrine, Norepinephrine, Ephedrine) are rarely indicated in the management of hemorrhagic shock
• Should only be used when adequate volume has been achieved, hemorrhage is controlled but hypotension continues

Uterine Atony (Tone)

• To identify uterine atony early, it is recommended to assess the abdominal uterine tone postpartum
• Massage and/or compression of the uterus or rubbing the uterine fundus and Oxytocin should be administered if the uterus is found to be atonic
  • Bimanual massage (one hand pressing on the fundus while the 2nd hand is placed anterior to the cervix) with the urinary bladder empty should be performed until therapeutic agents take effect or surgical intervention is started
• Aortic compression done after vaginal birth is recommended as a temporizing measure until necessary interventions are available
• Ergometrine, Methylergometrine, Carboprost, Misoprostol or Tranexamic acid may be given if the uterus is still atonic even after administration of Oxytocin
• A single dose of SL Misoprostol 800 mcg is a safe and effective treatment of PPH due to uterine atony in women with or without Oxytocin prophylaxis during the 3rd stage of labor
• Uterine balloon tamponade (UBT) may be done to control active PPH due to uterine atony that has failed to respond to 1st-line interventions and medical therapy
  • May arrest or stop bleeding in 75-95% of cases that do not need any further surgical therapy
  • Creates an outward pressure that compresses the vascular bed in the distended uterus which stops bleeding
  • Vaginal packing used to hold the balloon in place may obscure ongoing bleeding
  • WHO recommends the use of UBT in situations wherein surgical intervention and blood products are accessible if needed, and health personnel skilled in PPH management and use of UBT is available
• Intrauterine vacuum-induced tamponade may be a treatment option for rapid control of PPH 
  • A single-arm treatment study showed effectiveness at 94% 
  • Sucks blood from the uterine cavity and contracts the uterus constricting the myometrial blood vessels which stops bleeding 
  • Blood loss is quantified in real time and does not require vaginal packing
• Non-pneumatic anti-shock garment (NASG) is a first-aid garment compression device that can significantly improve shock or hemodynamic instability, decrease blood loss, reduce emergency hysterectomy for atony and decrease maternal mortality
  • Also a temporizing measure, NASG aids in stabilizing the patient which allows definitive medical and surgical management or transfer to more specialized centers
• Uterine artery embolization is done if there is persistent bleeding after other medical and non-surgical measures have been tried
  • An option for stable women before undergoing surgical intervention, particularly in situations wherein surgery is deemed difficult (eg severe obesity, placental previa, accreta, or presence of suspected intra-abdominal adhesions) 

Retained Products of Conception (Tissue)

• Manual exploration of the uterus is performed for possible retained placental tissue
  • Procedure should be performed under general anesthesia unless patient is in profound shock or an epidural is already in place
• Manual evacuation is done with hand passed through the cervix and into the lower segment, though retained products of conception may need surgical evacuation
• Therapeutic uterotonics are maintained throughout the procedure
• Broad-spectrum antibiotics are recommended after manual removal and in patients with endometritis-related secondary PPH
• Curettage may also be done for removal of retained products of conception

Genital Tract Trauma (Trauma)

• Trauma is the most likely cause of persistent bleeding despite a well-contracted uterus
• Direct visualization and inspection of the entire cervix aided by ring forceps is performed under appropriate analgesia and repair is undertaken for any laceration
• Pressure is applied over the laceration and must be observed for bleeding after repair
• Tranexamic acid may be given if Oxytocin or other uterotonics are unable to stop the bleeding or if the bleeding is partly due to trauma
• If immediate reversion cannot be done in patients with uterine inversion, stabilize the patient and perform uterine relaxation in the operating room

Coagulopathy (Thrombin)

• Please refer to Blood Transfusion
• Treat underlying disease with appropriate blood product replacement, restore intravascular volume and monitor coagulation status
• Recombinant factor VIIa and other medications promoting clot formation may be given as indicated, though it is not recommended to use recombinant factor VIIa routinely 
• It is advised to have patient’s factor levels >0.5 U/mL for 3-4 days following vaginal delivery and 4-5 days following a cesarean section 
  • Baseline factor levels should be obtained a few months postdelivery and lactation in women with bleeding disorders who initially presented during pregnancy 
• Patients with late PPH may be managed with Tranexamic acid and oral contraceptives
• Further evaluation is recommended for patients who do not respond to the usual treatment procedure, do not form blood clots or those in whom blood oozes from puncture sites
  • Platelet count, prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen and fibrin split products should be determined

Other

Management for Anemia

• Most patients with persistent bleeding are at risk for anemia
• If indicated, iron supplement should be advised for at least 3 months postpartum
• In women with moderate to severe postpartum anemia, may administer IV iron based on calculated iron deficiency

• Life-threatening hemorrhage which occurs when previous management with fundal massage, bimanual uterine compression, use of uterotonics and non-surgical treatment modalities failed to control or reduce bleeding 
• Requires urgent surgical intervention 
• Surgical therapy is directed to the cause of bleeding:
  • For atony, the following may be performed: B-Lynch compression suture and variants, uterine artery ligation, ovarian vessel ligation, bilateral internal iliac artery ligation
  • For uterine rupture: Laparotomy and primary repair
  • For placenta accreta: Surgical removal via laparotomy
  • Incision and evacuation of vaginal hematoma
• Compression sutures
  • Eg B-Lynch, Hayman, Pereira, Cho, Ouahba, Hackethal, Massuba
  • Slows bleeding and aids in stabilizing the patient 
  • Have a hemostatic success rate of 76-100% 
• Uterine artery ligation
  • Recommended when medical and non-surgical measures and compression sutures are unsuccessful 
  • Temporarily slows blood flow to the uterus, also preserves fertility 
  • With success rates described at 42% and 88% 
• Bilateral internal iliac artery ligation
  • Recommended when medical and non-surgical measures and compression sutures are unsuccessful 
  • Effective at controlling bleeding but requires a skilled and experienced surgeon 
  • Success rates of ≥75% are reported by several case series
• Hysterectomy
  • Performed in patients with massive hemorrhage when all other medical, non-surgical and surgical measures have failed
  • Commonly indicated for placental (eg placental abruption, placenta previa, abnormal placentation) and uterine (eg atony, rupture) disorders