INTRODUCTION — Postpartum hemorrhage (PPH) is an obstetrical emergency that can follow vaginal or cesarean delivery. It is a major cause of maternal morbidity, and one of the top five causes of maternal mortality in both high and low per capita income countries, although the absolute risk of death is much lower in high income countries (1 in 100,000 versus 1 in 1000 births in low income countries) [1].

INCIDENCE — The incidence of PPH varies widely, depending upon the criteria used to define the disorder. A reasonable estimate is 1 to 5 percent of deliveries [1,2].

DEFINITION AND DIAGNOSIS — PPH is best defined and diagnosed clinically as excessive bleeding that makes the patient symptomatic (eg, lightheadedness, vertigo, syncope) and/or results in signs of hypovolemia (eg, hypotension, tachycardia, or oliguria) (table 1).

Other definitions that have been proposed have been problematic. The most common definition of PPH is estimated blood loss ≥500 mL after vaginal birth or ≥1000 mL after cesarean delivery. The inadequacy of this definition was illustrated in studies that assessed blood loss using various objective methods: the mean blood loss reported after vaginal and cesarean deliveries was approximately 400 to 600 mL and 1000 mL, respectively, and clinicians were more likely to underestimate than overestimate the volume of blood lost [3-5].

Another classic definition of PPH is a 10 percent decline in postpartum hemoglobin concentration from prepartum levels. However, this is not a clinically useful definition for several reasons: rapid blood loss may trigger a medical emergency prior to observation of a fall in hemoglobin concentration; laboratory changes that are not correlated with events that endanger the patient should not be used to define a medical emergency; and prepartum hemoconcentration (eg, from preeclampsia or dehydration) may cause a large fall in serum hemoglobin concentration following delivery in the absence of excessive intrapartum blood loss.

PPH is also defined as primary or secondary: primary PPH occurs within 24 hours after delivery (also called early PPH) and secondary PPH occurs 24 hours to 12 weeks after delivery (also called late PPH).

Differential diagnosis — The findings of lightheadedness, vertigo, syncope, oliguria, tachycardia, or hypotension following delivery almost always indicate PPH. Although vasovagal reactions and vasodilatation due to drugs may also result in these symptoms, this is less common immediately postpartum, readily reversible, and generally not dangerous. In particular, pressor drugs should not be administered to a heavily bleeding patient under the mistaken belief that lightheadedness, tachycardia, or hypotension are due to an epidural block. An epidural block is unlikely to be the cause of these signs/symptoms if the woman was stable hemodynamically prior to delivery, the level of the block has not become significantly higher immediately following delivery, and her symptoms did not abruptly follow systemic administration of a drug known to cause hypotension. (See "Adverse effects of neuraxial analgesia and anesthesia for obstetrics", section on 'Hypotension'.)

ETIOLOGY AND RISK FACTORS — Bleeding after delivery is controlled by a combination of (1) contraction of the myometrium, which constricts the blood vessels supplying the placental bed, and (2) local decidual hemostatic factors, including tissue factor [6,7], type-1 plasminogen activator inhibitor [8,9], and systemic coagulation factors (eg, platelet and circulating clotting factors). Deficient contraction of the myometrium is manifested clinically as uterine atony. Defective decidual hemostasis is associated with inadequate decidualization (eg, placenta accreta) or bleeding diatheses (eg, factor deficiencies or thrombocytopenia). The major etiologies of and risk factors for PPH are described below:

Atony — The most common cause of PPH is uterine atony (ie, lack of effective contraction of the uterus after delivery), which complicates 1 in 20 births and is responsible for at least 80 percent of cases of PPH [10,11]. An atonic uterus may be related to:

• Overdistension (multiple gestation, polyhydramnios, macrosomia)
• Uterine infection
• Drugs (uterine relaxants)
• "Uterine fatigue" after a prolonged or induced labor
• Uterine inversion (see "Puerperal uterine inversion")
• Retained placenta (either a normally attached placenta or placenta accreta).

If the uterus appears to be firmly contracted after delivery, then other etiologies of hemorrhage should be considered. However, one should keep in mind that a focal area of the uterus can be atonic, which is difficult to appreciate on physical examination, or the uterus may not be maximally contracted.

Trauma — Trauma-related bleeding can be due to lacerations (perineal, vaginal, cervical, uterine), incisions (hysterotomy, episiotomy), or uterine rupture. Lacerations are more common after instrumental delivery.

Coagulation defects — Acquired and congenital bleeding diatheses may be associated with thrombocytopenia and/or hemostatic defects. Acquired causes include severe preeclampsia, HELLP syndrome, abruptio placentae, fetal demise, amniotic fluid embolism, and sepsis (see individual topic reviews on each subject). Consumptive coagulopathy may develop in women with severe hemorrhage.

Risk factors — A study including 154,311 deliveries compared 666 cases of PPH to controls without hemorrhage [12]. Factors significantly associated with hemorrhage, in decreasing order of frequency, were:

• Retained placenta (OR 3.5, 95%CI 2.1-5.8)
• Failure to progress during the second stage of labor (OR 3.4, 95%CI 2.4-4.7)
• Placenta accreta (OR 3.3, 95%CI 1.7-6.4)
• Lacerations (OR 2.4, 95%CI 2.0-2.8)
• Instrumental delivery (OR 2.3, 95%CI 1.6-3.4)
• Large for gestational age newborn (eg, >4000 g) (OR 1.9, 95%CI 1.6-2.4)
• Hypertensive disorders (OR 1.7, 95%CI 1.2-2.1)
• Induction of labor (OR 1.4, 95%CI 1.1-1.7)
• Augmentation of labor with oxytocin (OR 1.4, 95%CI 1.2-1.7)

In addition to the risk factors cited above, placenta previa, history of previous PPH, obesity, high parity, Asian or Hispanic race, precipitous labor, and preeclampsia, have been associated with PPH [1,11,13]. However, only a small proportion of women with any risk factors for PPH develop the disorder and many women without risk factors experience hemorrhage after delivery; thus, knowledge of risk factors is not very useful clinically.

Women with von Willebrand disease or factor XI deficiency or who are hemophilia carriers are at increased risk of both early and late PPH (16 to 22 percent for early and 11 to 24 percent for late) [14-17]. However, PPH alone is not a strong indication for screening for these defects, given that bleeding disorders are rarely the cause of PPH. As an example, one study of 50 women with PPH who underwent postpartum screening identified a bleeding diathesis in only one woman [18]. However, unexplained postpartum hemorrhage that does not respond to general measures should alert clinicians to the possibility of a bleeding disorder as a causative factor [19], especially in women with a history of menorrhagia, excessive bleeding after minor trauma, or a family history of a bleeding disorder. (See "Approach to the adult patient with a bleeding diathesis".)

COMPLICATIONS — PPH is a major cause of maternal morbidity, with sequelae such as shock, renal failure, and acute respiratory distress syndrome (table 2).

Sheehan's syndrome (ie, postpartum hypopituitarism) is a rare, but potentially life threatening, complication. The pituitary gland is enlarged in pregnancy and prone to infarction from hypovolemic shock. Damage to the pituitary can be mild or severe, and can affect the secretion of one, several, or all of its hormones. A common presentation is failure to lactate and amenorrhea/oligomenorrhea, but any of the manifestations of hypopituitarism (eg, hypotension, hyponatremia, hypothyroidism) can occur anytime from the immediate postpartum period to years after delivery. If the patient remains hypotensive after control of hemorrhage and volume replacement, she should be evaluated and treated for adrenal insufficiency immediately; evaluation of other hormonal deficiencies can be deferred until four to six weeks postpartum. (See "Clinical manifestations of hypopituitarism" and "Diagnosis of hypopituitarism".)

Another rare, but life threatening, complication is abdominal compartment syndrome (organ dysfunction caused by intraabdominal hypertension). The diagnosis should be considered in patients with a tensely distended abdomen and progressive oliguria who are developing multiorgan failure. (See "Abdominal compartment syndrome".)

OVERVIEW OF MANAGEMENT — It is important to coordinate activity among the individuals involved in treating women with PPH: obstetrical providers, nurses, anesthesiologists, hematologists, and blood bank personnel [20]. The obstetrical provider should initiate a sequence of nonoperative and operative interventions (table 3) for control of PPH and promptly assess the success or failure of each measure.

If an intervention does not succeed, the next treatment in the sequence must be swiftly instituted. Indecisiveness delays therapy and results in excessive hemorrhage, which eventually causes dilutional coagulopathy and severe hypovolemia, tissue hypoxia, hypothermia, and acidosis. This will make control of hemorrhage much more difficult and will increase the likelihood of hysterectomy, major morbidity from hemorrhagic shock, and death.

Development of a standardized institutional approach to management of PPH appears to improve outcome. For example, the California Maternal Quality Care Collaborative has established best practices for management of obstetrical hemorrhage (available at www.cmqcc.org/ob_hemorrhage/ob_hemorrhage_compendium_of_best_practices) and New York has published a health advisory with recommendations to providers for reducing the risk of maternal death from hemorrhage (available at www.health.state.ny.us/professionals/protocols_and_guidelines/maternal_hemorrhage/)

INITIAL INTERVENTIONS — We suggest the following procedures for initial management upon diagnosis of excessive vaginal bleeding after vaginal delivery:

Fundal massage — Begin fundal massage, which stimulates the uterus to contract.

Intravenous access — Ensure intravenous access, preferably with two large bore catheters (at least 18 gauge), for fluids, blood, and medications.

Uterotonic drugs — Since atony is the most common cause of PPH, uterotonic drugs are administered for presumed atony until a therapeutic effect is observed. An oxytocin infusion is usually already running, but the rate can be increased (eg, to 500 mL/hour). We promptly proceed with one dose of methylergonovine and then up to two doses of carboprost tromethamine 15 minutes apart. Some clinicians prefer to give the carboprost tromethamine first, or even omit the methylergonovine altogether. Many others prefer administration of misoprostol as the first-line drug after oxytocin.

There is no evidence that one sequence is better than another. The important point is not the sequence of drugs, but the prompt initiation of uterotonic therapy and the prompt assessment of its effect. It should be possible to determine within 30 minutes whether pharmacological treatment will reverse uterine atony. If it does not, prompt operative intervention is usually warranted.

• Oxytocin 40 units in 1 liter of normal saline intravenously or 10 units intramuscularly (including directly into the myometrium). Higher doses of oxytocin (up to 80 units in 1000 mL) can be administered intravenously for a short duration to manage uterine atony [21].
• Methylergonovine 0.2 mg intramuscularly (including directly into the myometrium) (never intravenously) if no hypertension, Raynaud's phenomenon, or scleroderma. May repeat at two to four hour intervals if there has been a good response to the first dose, otherwise move on to a different uterotonic agent.
• Carboprost tromethamine (15 methyl-PGF2alpha)(Hemabate) 250 mcg intramuscularly (including directly into the myometrium) every 15 to 90 minutes, as needed, to a total cumulative dose of 2 mg (8 doses), if no asthma. About 75 percent of patients respond to a single dose, move on to a different uterotonic agent if no response after several doses.
• Misoprostol (PGE1) is also effective, although data are more limited and the optimum dose and route are unclear [22]. Unlike methergine and carboprost, misoprostol can be given to women with hypertension or asthma. Various doses have been used: 800 or 1000 mcg rectally [23,24]; 200 mcg orally plus 400 mcg sublingually [25]; and 200 mcg orally plus 400 mcg sublingually plus 400 mcg rectally [26]. Maternal temperature should be monitored closely as pyrexia ≥40 degrees Centigrade can occur at these doses.

Dinoprostone (PGE2) 20 mg vaginal or rectal suppository, which can be repeated in two hours, is an alternative PGE to misoprostol (PGE1).

• Carbetocin, a long-acting analog of oxytocin, is in use in many countries (but not the United States) for prevention of uterine atony and hemorrhage. In this capacity, it appears to be as effective as oxytocin [27]. Carbetocin 100 mcg is given by a single slow intravenous injection. The toxicity spectrum is similar to that of oxytocin. It seems reasonable to use this drug as an alternative to oxytocin in countries where it is available, as it is easy to administer and has a short duration of action, but its efficacy in treating existing uterine atony is not well documented.

Fluid resuscitation and transfusion — Infuse a large volume of crystalloid to prevent hypotension (target systolic pressure 90 mmHg) [28]. A typical ratio is 3:1, ie, 3 liters of crystalloid for each 1 liter of estimated blood loss. However, replacement of blood components is more important than crystalloid infusion if massive hemorrhage has occurred or is likely [29]. Women with preeclampsia may have a contracted intravascular volume and hemoconcentration, thus they are particularly prone to the tissue hypoperfusion from blood loss. A bladder catheter with urimeter should be inserted to monitor urine output; intravenous fluids should maintain urine output at >30 mL/hour.

There are no universally accepted guidelines for replacement of blood components [30,31]. Recommendations are usually based upon expert opinion since there is no good evidence from randomized controlled trials. When laboratory data are available, most providers will transfuse patients with hemoglobin values less than 7.5 to 8 g/dL [32]. Before laboratory studies are available, we suggest transfusion of two units of packed red blood cells (pRBCs) if hemodynamics do not improve after the administration of 2 to 3 liters of normal saline and continued bleeding is likely. In addition, aggressive use of plasma replacement is important to reverse dilutional coagulopathy [33].

There is no consensus on the optimal ratio of blood product replacement; recommendations for RBC:fresh frozen plasma (FFP): platelet ratios vary widely [30,34,35]. Recent clinical experience in Iraq and Afghanistan, as well as domestic trauma centers, suggest administration of 1 unit of FFP for every 1 to 2 units of RBCs until the clinical situation is stable or absence of coagulopathy is confirmed by laboratory studies (see target levels below) [29,36].

A massive transfusion protocol is useful; several variations exists. The massive transfusion protocol for trauma and obstetrical services at Stanford University Medical Center utilizes an initial package consisting of 6 units RBCs, 4 units FFP, and 1 apheresis platelet unit [35]. At Brigham and Women's Hospital, the protocol calls for immediate availability of 2 units RBCs and 2 units FFP, followed by prompt administration of 4 units RBCs and 2 units each of FFP and platelets.

Virus- inactivated fibrinogen concentrate (RiaSTAP) may be used when fibrinogen levels are critically low (ie, <100 mg/dL) and FFP is not available. (See "Massive blood transfusion".)

We draw laboratory studies every 30 minutes to guide blood product replacement. We continue to transfuse RBCs, platelets, cryoprecipitate, and FFP to achieve the following targets:

• Hematocrit greater than 21 percent
• Platelet count greater than 50,000/uL
• Fibrinogen greater than 100 mg/dL
• Prothrombin (PT) and partial thromboplastin time (PTT) less than 1.5 times control

As an example, 4 units of FFP are given if the INR is more than 1.5, one apheresis platelet pack is given if the platelet count is less than 50,000, and 10 bags of cryoprecipitate are given if the fibrinogen is less than 100 mg/dL (table 4). A hemoglobin level of at least 8.0 g/dL after transfusion has been recommended since values below this level can be associated with impaired hemostasis from lower platelet adhesion and high blood velocity [37], as well as myocardial ischemia [28]. Transfusion is rarely indicated when the hemoglobin is greater than 10 g/dL [38].

The following UpToDate topic reviews discuss blood transfusion therapy in detail:

• (See "Indications for red cell transfusion in the adult".)
• (See "Management of shock in adult trauma".)
• (See "Use of red blood cells for transfusion".)
• (See "Massive blood transfusion".)

The Blood Bank should have compatible blood available for obstetric emergencies, and eliminate barriers to rapid access of uncrossmatched blood when needed [20].

Issues relating to Jehovah's Witnesses and others who are unwilling to accept transfusions are addressed in a separate topic review. (See "Approach to the patient who refuses blood transfusion".)

Laboratory tests — Baseline laboratory evaluation should include a complete blood count and coagulation studies (fibrinogen concentration [39], platelet count, prothrombin time, activated partial thromboplastin time). It is important to remember that the initial hemoglobin value does not reflect the amount of blood loss. Coagulation studies are usually normal initially, but may be abnormal in the presence of abruptio placentae, liver disease, intrauterine fetal demise, sepsis, or amniotic fluid embolism. Eventually massive hemorrhage without replacement of coagulation factors will result in coagulation abnormalities.

SECONDARY INTERVENTIONS — If the initial interventions described above are not immediately successful in controlling hemorrhage, we examine the birth canal with the woman in stirrups in a room with facilities for general anesthesia and both vaginal and abdominal surgery. The primary source of bleeding, uterine or lower genital tract, can usually be readily determined by visualizing the birth canal and by palpating the uterus. Adequate assistance, exposure, lighting, instruments, and anesthesia are necessary to perform a thorough examination.

Ideally, hemostatic defects will have been corrected prior to invasive interventions, but this can be difficult in the presence of continuous brisk hemorrhage. In such cases, blood product replacement concurrent with initiation of invasive procedures is necessary. An invasive intervention such as arterial embolization, balloon tamponade, uterine compression sutures, or uterine devascularization successfully controls hemorrhage in 85 to 90 percent of cases [40].

Provide adequate anesthesia — Local anesthesia may not provide sufficient pain relief for thorough examination and treatment; regional or general anesthesia should be administered to allow the patient to be comfortable. The choice of anesthetic depends upon the patient's hemodynamic status and planned interventions, and should be made in consultation with an anesthesiologist.

Inspect for and repair cervical and vaginal lacerations — The entire birth canal from perineum to cervix should be inspected for significant lacerations and the uterine cavity should be palpated for defects indicating uterine rupture or dehiscence. This examination should be performed in all patients who delivered vaginally, as well as those who attained significant cervical dilatation and descent of the presenting fetal part before a cesarean delivery. Even if inspection for lacerations was already done at delivery, a thorough examination should be repeated as it is possible that a bleeding site was missed. Risk factors for significant cervical lacerations (ie, associated with excessive bleeding or requiring repair) include precipitous labor, operative vaginal delivery, and cerclage [41].

Heavily bleeding vaginal and cervical lacerations are repaired with a running locked #0 absorbable suture. Exposure is facilitated by using a Gelpi retractor (figure 1) to spread the distal vaginal sidewalls and Heaney (figure 2) or Breisky (figure 3) retractors to access the upper vagina. It is often difficult to begin a suture line at the apex of the laceration because of problems with exposure and visualization. In such cases, one can begin the suture line at the distal end of the laceration and sew toward the apex, while using the suture line to pull the lacerated tissue towards the surgeon.

Two pitfalls should be avoided:

• Sutures should not be placed superior to the fornix, as this can result in ureteral ligation. When such extension exists, laparotomy should be performed with the woman's thighs abducted in stirrups, thus allowing surgery to proceed simultaneously via the abdominal and vaginal routes. This will facilitate identification of the bladder and ureters, minimizing the chance of inadvertent damage.
• Vaginal hematomas should not be drained unless expanding. Attempts at operative drainage can result in significant additional blood loss because it is often difficult to identify and ligate bleeding vessels in a fresh vaginal sulcus hematoma. A stable hematoma may be drained if it becomes infected or pain is not relieved adequately with analgesics. Continuous expansion of a hematoma leading to hypovolemia may necessitate drainage and packing. Management of vaginal hematomas is discussed in more detail separately. (See "Evaluation and management of lower genital tract trauma in women".)

Issues pertaining to repair of uterine rupture are reviewed elsewhere. (See "Trial of labor after cesarean delivery", section on 'Uterine rupture'.)

Remove retained products of conception — The uterus should be explored and any retained placental fragments or fetal membranes should be removed manually, if possible, or with ring forceps. Ultrasound examination can be helpful for diagnosis of retained tissue and to guide removal [42]. Curettage with a 16 mm suction catheter or (preferably) a large blunt curette (banjo curette) is performed if manual removal is unsuccessful in controlling hemorrhage.

Uterine tamponade — Uterine tamponade is effective in many patients with atony or lower segment bleeding. However, in the setting of cardiovascular instability, it is important to avoid prolonged, futile attempts at temporizing measures rather than proceeding to laparotomy and, if necessary, hysterectomy.

Either a balloon or a pack can be used [43]. Regardless of the form of tamponade employed, the hemoglobin and urine output should be closely monitored. This is especially important when a gauze pack is used because a large amount of blood can collect behind the pack. The distended tamponaded uterus causes discomfort, which can be treated with analgesics or a slight reduction in distending pressure, as long as tamponade is maintained [43].

Devices used to tamponade the uterus are removed after 24 hours. Deflation is performed slowly, eg. 20 mL/hour.

• Balloons — The Bakri tamponade balloon was specifically designed for uterine tamponade to control postpartum bleeding. It is a silicone balloon with a capacity of 500 mL of saline, and strength to withstand a maximum internal and external pressure of 300 mmHg (figure 4) [44]. The balloon is filled until bleeding is controlled.

The BT-Cath (Utah Medical) was also developed specifically for uterine tamponade. After the silicone balloon is inserted into the uterine cavity, one lumen of the duel lumen catheter is used to infuse saline and expand the balloon, while the other lumen allows drainage of blood from the fundus. The inverted pear shape of the balloon conforms to the shape of the uterus, which helps prevent the balloon from being expelled.

A Sengstaken-Blakemore tube can also be used to tamponade the uterus [45-47]. This not only tamponades the uterus, but allows for drainage of blood from sites proximal to the tube. Excessive bleeding suggests that tamponade is not effective. In two series of patients with massive PPH, use of a Sengstaken-Blakemore tube reduced the need for surgery or embolization in most patients and was also useful for controlling bleeding while patients waited for such procedures [47,48]. Both the gastric and the esophageal balloons have been used successfully.

If these devices are not available, a #24 Foley catheter with a 30 mL balloon can be guided into the uterine cavity and inflated with 60 to 80 mL of saline as an alternative means of tamponading the uterus. A condom catheter or Rusch balloon catheter are other options.

Uterotonic agents are usually administered, but there is no evidence that this is useful during tamponade.

• Packs — Uterine packs also have been used to control PPH with variable success; proper technique requires firmly packing the entire uterine cavity with gauze, such as Kerlix, to achieve tamponade [49-51]. The gauze can be impregnated with 5000 units thrombin in 5 mL sterile saline to enhance clotting. A regimen of intravenous broad spectrum antibiotics, such as gentamicin, 1 mg/kg every eight hours, and either metronidazole, 500 mg every eight hours, or clindamycin, 300 mg every six hours, are administered while the pack is in place. If packing does not control hemorrhage, repacking is not advised [52].

Arterial embolization — Arterial embolization by an interventional radiologist is an option if the woman is hemodynamically stable and personnel and facilities are readily available. A selective procedure is done when a single bleeding vessel is identified and can be occluded. Alternatively, if the area of bleeding is diffuse or a single bleeding vessel cannot be identified, then a large artery that feeds multiple smaller vessels in the area that is bleeding can be occluded. As an example, bilateral internal iliac arteriography is performed through a catheter inserted into a femoral artery. An occlusive thrombotic agent is fed through the catheter to obliterate arteries feeding sites of extravasation; both uterine arteries usually must be occluded. This procedure is discussed in detail separately. (See "Interventional radiology in management of obstetrical and gynecological disorders", section on 'Postpartum hemorrhage'.)

Case reports and small case series have consistently reported that menstrual function and fertility return to baseline after arterial embolization for PPH, and subsequent pregnancies do not experience any increase in adverse outcome [53-60]. This experience appears to contradict the reports describing increased pregnancy loss after uterine artery embolization for treatment of leiomyomas. Possible reasons for this discordancy include the typically younger age of pregnant patients, the vastly increased vascularization of the gravid uterus (possibly permitting formation of more adequate alternative blood supply), and the absence of leiomyomas in the gravid patients. It is also possible that arterial embolization of the gravid uterus is associated with an increased incidence of subsequent pregnancy loss above baseline, but the absence of systematic study has failed to discover this.

Laparotomy — If vital signs are worse than expected for the estimated blood loss, the possibility of internal hemorrhage should be considered, particularly in women who had an operative delivery or are otherwise at risk of uterine rupture.

Laparotomy to assess and treat bleeding in the pelvis should be performed through a vertical midline incision. A self-retaining retractor, such as a Balfour, provides adequate lateral exposure. Uterine atony and sites of extrauterine bleeding can usually be identified without difficulty. If a discrete vessel is responsible for hemorrhage, it is clamped and ligated with appropriate suture material. Atony or bleeding adjacent to the uterus that is difficult to control is treated by ligation of uterine vessels (see below). If this is not effective, other surgical options should be tried:

Uterine vessel ligation — Bilateral ligation of the uterine vessels (O'Leary stitch) to control PPH has become the first-line procedure for controlling uterine bleeding in the parturient at laparotomy [61,62]. It is a more attractive option than internal iliac artery ligation (see below) because the uterine arteries are easily accessible, the procedure is more successful, and the field of dissection generally is not near the ureters and the iliac veins.

After identification of the ureter, a #0 chromic catgut or polyglycolic acid suture on a large curved needle is passed through the lateral aspect of the lower uterine segment as close to the cervix as possible, then back through the broad ligament just lateral to the uterine vessels. It is then tied to compress these vessels (figure 5).

If this does not succeed in controlling bleeding, the vessels of the utero-ovarian arcade are similarly ligated just distal to the cornua by passing a suture ligature through the myometrium just medial to the vessels.

Ligation of all four arteries and veins reportedly is successful in controlling hemorrhage in over 90 percent of patients [62,63]. Uterine necrosis and placental insufficiency in a subsequent pregnancy have not been described as complications [63,64]. However, there is a single case report of ovarian failure and development of intrauterine synechiae after postpartum ligation of the uterine, utero-ovarian, and ovarian arteries for PPH related to atony [65].

Uterine compression sutures — Uterine compression sutures are an effective method for reducing PPH and avoiding hysterectomy. Limited follow-up of women who have had a uterine compression suture suggests that there are no adverse effects on future pregnancy [66].

The B-Lynch suture envelops and compresses the uterus, similar to the result achieved with manual uterine compression [67]. In case reports and small series, it has been highly successful in controlling uterine bleeding from atony when other methods have failed [67-71]. The technique is relatively simple to learn, appears safe, and preserves future reproductive potential.

A large Mayo needle with #2 chromic catgut is used to enter and exit the uterine cavity laterally in the lower uterine segment (figure 6). The suture is looped over the fundus and reenters the lower uterine cavity through the posterior wall. The suture then crosses to the other side of the lower uterine segment, exits through the posterior wall, and is looped back over the fundus to enter the anterior lateral lower uterine segment opposite and parallel to the initial bites. The free ends are pulled tightly and tied down securely to compress the uterus, assisted by bimanual compression.

Other techniques which have been reported in small case series represent modifications of the B-Lynch suture [69,72-78]. Hayman described placement of two to four vertical compression sutures from the anterior to posterior uterine wall without hysterotomy (figure 7) [72,73]. A transverse cervicoisthmic suture can also be placed if needed to control bleeding from the lower uterine segment. Pereira described a technique in which a series of transverse and longitudinal sutures of a delayed absorbable multifilament suture are placed around the uterus via a series of bites into the subserosal myometrium, without entering the uterine cavity (figure 8) [74]. Two or three rows of these sutures are placed in each direction to completely envelope and compress the uterus. The longitudinal sutures begin and end tied to the transverse suture nearest the cervix. When the transverse sutures are brought through the broad ligament, care should be taken to avoid damaging blood vessels, ureters, and fallopian tubes. The myometrium should be manually compressed prior to tying down the sutures to facilitate maximal compression.

The specific placement of compression sutures is determined by the operator at the time of laparotomy, and their location requires operator judgment. Generally, longitudinal sutures should be easier to place, and should be safer, than transverse sutures, but this may not always be the case. Complications, such as uterine necrosis, have been reported rarely [79].

Internal iliac artery ligation — Bilateral ligation of the internal iliac arteries (hypogastric arteries) has been used to control uterine hemorrhage by reducing pulse pressure of blood flowing to the uterus [80]. The technique is difficult, especially with a large uterus, a small transverse incision, a pelvis full of blood, and a surgeon who rarely operates in the pelvic retroperitoneal space [81]. For these reasons, uterine artery ligation has largely replaced this procedure.

Internal iliac artery ligation should be considered only after attempts to ligate the uterine and ovarian vessels have failed to control bleeding. A surgeon who does not frequently operate in the pelvic retroperitoneum probably should omit this procedure and proceed to hysterectomy unless consultation with a gynecologic oncologist, or other surgeon familiar with the procedure, is readily available. (See "Peripartum hysterectomy".)

• Procedure — On each side, the anterior leaf of the broad ligament is opened with Metzenbaum scissors and the areolar tissue of the retroperitoneum is lysed. The external iliac artery is readily identified at the medial margin of the psoas muscle, and is followed to the common iliac artery bifurcation. The internal iliac artery is about 4 cm in length before it divides into anterior and posterior branches. Nodal tissue overlying the internal iliac artery is dissected away by spreading the tissue with a tonsil clamp or the tips of Metzenbaum scissors. Ideally, the dissection is carried caudally to the anterior and posterior trunks of the internal iliac artery so that the anterior trunk can be selectively ligated. In practice, this is so difficult that the entire internal iliac artery usually is ligated about 2 cm distal to its origin. Careful spreading dissection with a right angle or tonsil clamp anterior and lateral to the internal iliac artery and then continuing the dissection around the artery in the same plane, proceeding dorsally, separates it from the internal iliac vein, which is slightly medial and posterior to the artery. A free ligature of #0 silk is carried around the internal iliac artery in a clamp from lateral to medial and is tied securely.

There are two important technical errors that are easy to commit, each of which may be detrimental:

• It is possible to mistakenly ligate the external iliac instead of the internal iliac artery. This usually leads to loss of the ipsilateral lower limb if not promptly corrected.
• The large, dilated, fragile internal iliac vein lies just behind and slightly medial to the artery and is often not visualized during isolation of the artery. Laceration of this vein can lead to rapid exsanguination. The external iliac artery lies lateral to the internal iliac artery and care should also be taken to avoid it.

A review of pregnancy outcome after internal iliac artery ligation for PPH described 49 pregnancies with no evidence of any increase in adverse events [82].

Additional measures

• Occasionally it is possible to control uterine hemorrhage from a partial placenta accreta by excising the implantation site and closing the uterine incision primarily. (See "Diagnosis and management of placenta accreta".)

• Injection of dilute vasopressin for intractable bleeding due to placenta accreta has resulted in cessation of bleeding without need for further surgery [83,84]. Vasopressin causes acute vasospasm, thus decreasing blood flow near the injection site and allowing coagulation to occur. Twenty units (one mL) of vasopressin is diluted with 100 mL normal saline to yield a 0.2 units/mL solution. One mL of this solution is then slowly infiltrated subendometrial at the bleeding site, taking great care to avoid direct intravascular injection.
• Severe bleeding may pose a threat of exsanguination within a few minutes. In these cases, the surgeon should palpate the aorta a few centimeters superior to the sacral promontory and compress the aorta just proximal to the bifurcation. This will markedly slow the volume of bleeding and affords a better opportunity for finding and controlling the source of hemorrhage.
• Intraoperative blood salvage with a leukocyte filter and autotransfusion is another option [85,86]. There is a theoretical concern of reinfusing amniotic fluid and causing amniotic fluid embolism, but this has been documented only once [87]. Its use remains investigational in this setting.

Recombinant activated factor VIIa — Human recombinant factor VIIa has been approved by the United States Food and Drug Administration for treatment of individuals with bleeding related to hemophilia A and B inhibitors, acquired inhibitors, and congenital factor VII deficiency. It has also been used successfully off-label for control of bleeding in other situations, such as intractable bleeding associated with postpartum uterine atony, placenta accreta, or uterine rupture [88]. This therapy appears promising when standard therapy fails [89].

Doses of 16.7 to 120 mcg/kg as a single bolus injection over a few minutes every two hours until hemostasis is achieved have been effective, and usually control bleeding within 10 to 40 minutes of the first dose [88,90]. However, the appropriate dose of rFVIIa may be quite different, depending on the levels of other coagulation factors present. As an example, a case report of bleeding despite administration of rFVIIa for PPH attributed the failure to the patient's low fibrinogen level (<60 mg/dL) [91]. The authors suggested aggressive therapy with standard blood components should be undertaken before giving rFVIIa. (See "Therapeutic uses of recombinant coagulation factor VIIa".)

The drug is very expensive (about $1 per mcg) and may increase the risk of thromboembolism.

Hysterectomy — Hysterectomy is the last resort, but should not be delayed in women who require prompt control of uterine hemorrhage to prevent death. Continued blood loss can lead to disseminated intravascular coagulation due to massive loss of coagulation factors. Severe hypovolemia, tissue hypoxia, hypothermia, and acidosis can result, which further compromise the patient's status. If the patient is not already at laparotomy and has developed these additional complications, then correction of the severe physiological deficits before hysterectomy could be life saving [92,93]. (See "Peripartum hysterectomy".)

Post-laparotomy inspection — At the completion of the laparotomy, the operative field should be inspected carefully for hemostasis. Following laparotomy, the bladder should be inspected and the ureters identified. If there is a possibility of bladder laceration, then 200 mL of saline mixed with 5 mL of indigo carmine can be infused into the bladder through the Foley catheter. Integrity of the bladder is confirmed by failure of the colored fluid to leak through the serosa.

The ureter should be identified before abdominal closure either by transillumination through the broad ligament or direct visual identification during retroperitoneal dissection (figure 9). It courses horizontally along the peritoneum 1 to 5 cm dorsal to the ovarian vessels and can be identified readily as it passes ventral to the bifurcation of the common iliac artery.

The ureters should be inspected to confirm that they are not damaged. Their integrity can be assessed by injecting two ampules (10 mL) of indigo carmine intravenously. A ureter that has been severed will release blue urine into the pelvis in 10 to 15 minutes. Cystoscopy or direct visualization of the ureters through a cystotomy will demonstrate that urine is only passing through one of the two ureteral orifices if a ureter has been ligated. Passage of a ureteral stent can be employed to localize the site of obstruction. (See "Cystoscopy".)

SECONDARY POSTPARTUM HEMORRHAGE — Secondary postpartum hemorrhage refers to excessive uterine bleeding occurring between 24 hours and 12 weeks postpartum. It affects 0.5 to 2 percent of women in developed countries [94,95]. The pathogenesis is thought to be diffuse uterine atony or subinvolution of the placental site secondary to retained products of conception and/or infection, but the exact cause is often not determined. The possibility of a bleeding diathesis, such as von Willebrand disease, should be considered, especially in women with a history of menorrhagia.

Bleeding typically is not as catastrophic as with primary hemorrhage. As with primary PPH, a previous history of secondary PPH appears to predispose to a recurrence [96-98].

There are no data from randomized controlled trials to guide management [94]. Medical therapies include uterotonic agents (see 'Initial interventions' above) and/or antibiotics (table 5). If the uterus is atonic, uterotonic agents are given. Options include oxytocin infusion, methylergonovine (0.2 mg intramuscularly, repeated every two to four hours up to three doses), or intramuscular carboprost tromethamine (Hemabate, 250 mcg intramuscularly; up to eight doses at intervals of no less than 15 minutes). However, these agents will not be useful if the uterus is firm.

If bleeding is not massive, and there is fever, uterine tenderness, or a foul-smelling discharge, then endometritis should be suspected. Under these circumstances, we prescribe broad spectrum antibiotic therapy. However, some clinicians administer antibiotics to all patients with secondary PPH, including those without obvious signs of infection. (See "Postpartum endometritis".)

Surgical procedures (D&C, suction curettage) are directed at evacuation of retained products and are often efficacious if the uterus is firm, or when medical management fails, even if retained placental or membrane fragments cannot be identified preoperatively [95,99]. As an example, a study of 132 consecutive women with secondary PPH reported 75 (57 percent) were initially treated with surgical evacuation, which was successful in 67 (90 percent) [95]. Of the 57 women initially managed medically, treatment was successful in 41 (72 percent), 16 women had continuing symptoms of whom 12 subsequently underwent surgical evacuation. Tissue specimens were obtained at surgery in 38 women and only one-third of these had histological confirmation of placental tissue.

Ultrasound examination may be helpful. In women with secondary PPH, an echogenic mass in an enlarged uterine cavity suggests retained placental tissue [100]. Fluid in the cavity or a mixed-echo pattern are more consistent with normal involution, although a mixed-echo pattern is sometimes associated with retained placental tissue.

Suction curettage should be employed when bleeding is over 500 mL and is not controlled by medical measures. The size of the suction cannula is determined by the size of the uterus. We use the diameter cannula corresponding to the uterine size by gestational age (eg, a 12 mm cannula for a uterus of 12 weeks size) with a minimum diameter of 10 mm and a maximum diameter of 16 mm.

Uterine perforation and formation of intrauterine adhesions are the major complications of surgery. In the series described above, perforation occurred in 3 percent of cases [95]. These complications emphasize the need to be selective in choosing candidates for surgical therapy. Unfortunately, sonographic evidence of accumulation of fluid and debris in the uterine cavity is a common finding in the involuting uterus and does not distinguish patients requiring surgical versus medical therapy [95,101,102]. (See "Intrauterine adhesions".)

TREATMENT OF POSTPARTUM ANEMIA — Postpartum anemia is treated with oral iron supplementation. A single 325 mg ferrous sulfate tablet taken orally three times daily between meals provides 195 mg of elemental iron per day. This regimen should lead to a modest reticulocytosis beginning in approximately seven days and a rise in the hemoglobin concentration of approximately 2 g/dL over the ensuing three weeks.

Although erythropoietin (EPO) can increase the rate of recovery to normal hemoglobin levels, it should not be used in an attempt to reduce transfusion requirements after PPH [103-105]. It has not been proven to reduce the frequency of transfusion and is no more effective than iron therapy in this setting since it does not have an immediate therapeutic effect. Furthermore, EPO is expensive and its use has been associated with an increased risk of venous thrombosis postoperatively.

Hemoglobin levels rise faster with parenteral iron therapy than with oral therapy, however, most women resolve their anemia sufficiently rapidly with oral iron [106,107]. Administration of parenteral iron is rarely indicated, given its risks (eg, anaphylaxis) and costs. If parenteral therapy is administered, ferric gluconate in sucrose complex and iron sucrose are safer than iron dextran.

The indications for red blood cell transfusion and parenteral iron therapy are discussed separately. These interventions may be needed instead of oral iron therapy in women who are unable to care for themselves or their newborns because of severe anemia. (See "Indications for red cell transfusion in the adult" and "Treatment of anemia due to iron deficiency".)

RECURRENCE AND PREVENTION — Women with a prior PPH have as much as a 10 percent risk of recurrence in a subsequent pregnancy [108,109]. Preventive measures are discussed separately. (See "Management of the third stage of labor".)

Labor and delivery units should consider compiling medications and instruments that may be needed to manage PPH so that this equipment is readily available when needed (similar to a "code cart"). The Joint Commission on Accreditation of Healthcare Organizations recommends that obstetrical staff periodically conduct clinical drills to help staff prepare for PPH, conduct debriefings to evaluate team performance, and identify areas for improvement [110].

SUMMARY AND RECOMMENDATIONS

• Postpartum hemorrhage can be defined as excessive bleeding that makes the patient symptomatic (eg, lightheadedness, vertigo, syncope) and/or results in signs of hypovolemia (eg, hypotension, tachycardia, or oliguria). (See 'Definition and diagnosis' above.)

• The most common causes are atony, trauma, consumptive coagulopathy, and bleeding diatheses. (See 'Etiology and risk factors' above.)

• Although there are many known risk factors for postpartum hemorrhage, knowledge of these risk factors is not clinically useful. (See 'Etiology and risk factors' above.)

• We recommend initial management of primary postpartum hemorrhage include fundal massage, placement of large bore intravenous lines and Foley catheter, crystalloid infusion, administration of uterotonic agents, and transfusion of blood products as needed (Grade 1B). We begin an oxytocin infusion and then promptly proceed with the following interventions one by one until the hemorrhage is controlled: one dose of methylergonovine and then up to two doses of carboprost tromethamine. Misoprostol administration after oxytocin is an alternative common and acceptable approach. (See 'Initial interventions' above.)

• If these measures do not control hemorrhage, we suggest secondary management include the following sequence of interventions: assessment for and repair of lacerations (if present), removal of retained placenta and fetal membranes, uterine balloon tamponade, and uterine artery ligation (Grade 2C). If selective arterial embolization is readily available, we suggest this procedure be considered before laparotomy for uterine artery ligation, given that embolization is a less morbid procedure and cannot be performed after ligation if ligation is unsuccessful (Grade 2C). A list of potential therapeutic interventions is provided in the table (table 6). (See 'Secondary interventions' above.)

• Hysterectomy is a last resort, but should not be delayed in women who have disseminated intravascular coagulation and require prompt control of uterine hemorrhage to prevent death. (See 'Hysterectomy' above.)

• For secondary postpartum hemorrhage, we suggest administration of uterotonic agents and/or antibiotics (Grade 2C). If unsuccessful, we suggest suction curettage to evacuate potential retained products of conception (Grade 2C). (See 'Secondary postpartum hemorrhage' above.)