Postpartum infectious complications: Clinical Guidelines

List of Abbreviations

Terms and Definitions

Abdominal sepsis is a pathological process based on the systemic inflammatory response of the body to an intra-abdominal infection, leading to acutely developed organ dysfunction.

Pelvic abscess is an abscess localized in the rectouterine pouch, occurring as a complication of acute inflammatory diseases, trauma, or surgeries of the pelvic or abdominal organs.

Surgical site infection (SSI) is a complication of the wound healing process resulting from the growth of microorganisms and leading to local and/or systemic manifestations.

Maternal sepsis is a pathological process based on the systemic inflammatory response of the body to an infection, leading to acutely developed organ dysfunction during pregnancy, childbirth, the post-abortion period, or the postpartum period.

Acute respiratory distress syndrome (ARDS) is an acutely developing diffuse inflammatory lesion of the lung parenchyma, developing as a non-specific reaction to various damaging factors and leading to acute respiratory failure due to impaired lung tissue structure and a decrease in the mass of aerated lung tissue.

Peritonitis is a broad complex of pathological processes occurring in the peritoneal cavity, peritoneum, underlying tissues (preperitoneal tissue, walls of abdominal organs and their lumina), as well as at the level of all vital organs and systems (systemic inflammatory response, sepsis, organ and system dysfunctions, shock).

Multiple organ failure is a severe non-specific stress response of the body, a combination of failure of several functional systems, developing as the terminal stage of most acute diseases and injuries.

Postpartum endometritis is an infectious inflammation of the endometrium occurring in the postpartum period. Most often, the myometrium is also involved in the inflammatory process.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection.

Septic shock is a type of sepsis in which the systemic inflammatory response of the body is accompanied not only by organ dysfunction, but also by persistent tissue hypoperfusion that is unresponsive to fluid resuscitation and requires vasopressor support.

Chorioamnionitis is an infectious inflammation of the fetal membranes and amniotic fluid caused by polymicrobial associations.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Postpartum infectious complications are diseases observed in postpartum women that are directly related to pregnancy and childbirth and caused by a bacterial infection (from the moment of delivery until the end of the 6th week postpartum). These clinical guidelines cover the following main postpartum infectious complications: surgical site infections, postpartum endometritis, obstetric peritonitis, postpartum sepsis, and septic shock.

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Surgical site infection (SSI) in most cases develops 4–7 days after surgical intervention [1]. SSI is a polyetiological infectious complication. Staphylococcus aureus is the most common microorganism, accounting for 15–20%. Microorganisms of the genus Enterococcus and Escherichia coli are of great importance in the etiology [2].

Risk factors for the development of SSI after cesarean section include: subcutaneous hematoma, chorioamnionitis, severe extragenital pathology, smoking during pregnancy, incision length >16.6 cm, BMI >30–35 kg/m², glucocorticosteroid use, subcutaneous fat thickness >3 cm, lack of antibiotic prophylaxis, gestational diabetes mellitus, duration of surgery ≥38 min, hypertensive disorders during pregnancy, premature rupture of membranes, history of cesarean section, emergency cesarean section [1,3–9].

The dependence of SSI manifestations on the virulence and number of microorganisms is well known. Highly virulent microorganisms play a predominant role in pathogenesis, leading to local tissue damage and delayed tissue repair [10,11]. However, the dynamic interaction between the host organism and the pathogen, which leads to the development of local and systemic manifestations, requires further study.

The International Wound Infection Institute has defined the stages of wound infection development [1].

1. Wound contamination is the presence of microorganisms in the wound that does not lead to local or systemic manifestations [10] and culminates in the development of immune responses, predominantly phagocytosis processes.

2. Colonization is the presence of limited microorganism growth that does not lead to local or systemic manifestations [12]. At the same time, a non-critical number of microorganisms is observed, which does not hinder the timely repair of the wound.

3. Local infection is a complication of the wound healing process in which an increase in microorganism growth leads to local and/or systemic manifestations [12].

4. Spread of infection is a complication of the wound healing process in which an increase in microorganism growth leads to their extension beyond the boundaries of the wound [13].

5. Systemic infection is a complication of the wound healing process in which the spread of infection throughout the body via the vascular or lymphatic systems leads to a systemic inflammatory response, sepsis, and organ dysfunction.

Postpartum endometritis has a polymicrobial nature [14]. In 60–70% of cases, the infection is caused by both aerobic and anaerobic flora. Among anaerobic pathogens, Peptostreptococcus, Peptococcus, Bacteroides, Prevotella and Clostridium are distinguished. Aerobic species are primarily represented by Streptococcaceae groups A and B, the order Enterobacterales, Enterococcaceae, Staphylococcaceae, Proteus and Escherichia coli species. Uterine tissues damaged during cesarean section are particularly susceptible to Streptococcus pyogenes and Staphylococcus aureus [15–18].

Risk factors for postpartum endometritis include chorioamnionitis, BMI >30 kg/m², prolonged labor, premature rupture of membranes, multiple vaginal examinations during labor, invasive cardiotocography, meconium-stained amniotic fluid, lack of antibiotic prophylaxis, young maternal age, low socioeconomic status, and bacterial colonization of the lower genital tract by such bacteria as Streptococcus agalactiae, Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Gardnerella vaginalis [18–22].

The most common risk factor for postpartum endometritis is Cesarean section [23,24].

This risk increases 21-fold, according to some sources [23], and 30-fold, according to others, in the case of emergency Cesarean section performed during labor [18].

The pathogenesis of postpartum endometritis remains currently incompletely understood. Early manifestation of postpartum endometritis is most often associated with microbial colonization of the amniotic fluid and decidua prior to delivery [25].

Furthermore, there is a correlation between inflammatory-infectious diseases and delayed involutional processes in the postpartum period.

The main pathways of infection spread in postpartum endometritis are:

a) ascending;

b) hematogenous (dissemination of bacteria from a primary extragenital focus);

c) lymphogenous (via the regional vascular system, facilitated by extensive endometrial defects and genital trauma);

d) intraamniotic, associated with the clinical use of invasive diagnostic methods [26].

In a physiological puerperal period, the placental site represents a large aseptic wound. Infiltration of the wound surface by leukocytes, epithelialization, and endometrial regeneration are observed without the formation of an inflammatory infiltrate and necrosis [27]. In the presence of predisposing factors, an inflammatory lymphocytic and leukocytic infiltrate develops in the wound surface area with gradual extension to the myometrium. If the disease progresses, the inflammatory process may spread to the serosal layer of the uterus, leading to pelvic abscess formation, pelvic thrombophlebitis, and the development of obstetric peritonitis [28].

Obstetric peritonitis is characterized by a polyetiological nature. According to the multicenter observational study of intra-abdominal infections worldwide (CIAOW), there is an increasing trend in the number of resistant microorganisms [29]. The main etiological factors may include Escherichia coli, Klebsiella pneumoniae, Enterococcus species, Pseudomonas species [30].

In the pathogenesis of obstetric peritonitis, a transition from an acute pro-inflammatory response to a mixed anti-inflammatory response with balanced pro- and anti-inflammatory mediators is observed. The subsequent onset of the compensatory anti-inflammatory response syndrome is one of the predisposing factors increasing the body's susceptibility to secondary infectious complications [31]. Peritonitis is accompanied by a persistent increase in intra-abdominal pressure, with values of ≥12 mm Hg. Abdominal compartment syndrome is characterized by a sustained increase in intra-abdominal pressure >20 mm Hg, leading to impaired tissue perfusion and contributing to decreased functional activity of organs up to their failure [32]. At the same time, a correlation is noted between increasing levels of intra-abdominal pressure and the risk of 28- and 90-day mortality [33].

Postpartum sepsis is a polyetiological disease that can be caused by most pathogenic and opportunistic microorganisms. The main causative agents of postpartum sepsis include Streptococcus pyogenes, Escherichia coli, Streptococcus pneumoniae, Clostridium septicum, Morganella morganii, Staphylococcus aureus [34]. Currently, there is an increase in the frequency of methicillin-resistant Staphylococcus aureus strains as an etiological factor of postpartum sepsis [37, 38].

Risk factors for postpartum sepsis include obesity, carbohydrate metabolism disorders (impaired glucose tolerance, diabetes mellitus), immune response disorders (receiving immunosuppressive therapy), anemia, a history of pelvic inflammatory disease, amniocentesis and other invasive procedures during pregnancy, cervical cerclage, prolonged rupture of membranes, birth trauma (vaginal lacerations), Cesarean section, postoperative wound hematoma, retained placental tissue or fetal membranes, and Group A β-hemolytic streptococcus infection in family members of the patient [36, 39–41].

The pathogenesis of sepsis at the cellular and molecular levels is extremely complex. Pathogen invasion into the body leads to the activation of innate immunity through interaction processes between pathogen-associated molecular patterns (PAMPs) and pattern-recognition receptors (PRRs), which lead to the synthesis of proinflammatory cytokines by macrophages [40–42].

[1] International Wound Infection Institute (IWII). Wound infection in clinical practice. Wounds International 2016

1.3 Epidemiology of the Disease or Condition

Despite successful management of infection in clinical medicine, sepsis and septic shock remain among the leading causes of death due to many medical, social, and economic factors [43–45].

According to WHO data (2014), the maternal mortality ratio resulting from purulent-septic complications in low- and middle-income countries is 10.7%, which is more than twice as high as this indicator in high-income countries (4.7%) [44].

According to the Global Maternal and Neonatal Sepsis Study (GLOSS, 2020), conducted in 52 countries, the incidence of maternal infection was 70.4 (95% CI 67.7–73.1) women per 1,000 live births, and the incidence of adverse outcomes (severe maternal outcomes "near miss" and maternal death) was 10.9 (95% CI 9.8–12.0) per 1,000 live births. The highest values were observed in low- and middle-income countries, and the lowest in high-income countries [46].

In the Russian Federation, septic complications rank fifth in the structure of maternal mortality. According to the Russian Ministry of Health, the proportion of septic complications showed an upward trend in 2018, accounting for 7.5% of the structure of maternal mortality [1].

According to the statistical compilation of the Russian Ministry of Health (main indicators of maternal and child health, activities of the child healthcare and obstetrics service in the Russian Federation), the incidence of widespread postpartum infection and sepsis among women was 1.31 in 2005, 0.51 in 2010, 0.19 in 2015, 0.17 in 2017, and 0.18 in 2018 per 1,000 births [2].

SSI complicates the postpartum period in 2–7% of patients [47,48].

Postpartum endometritis is the most common postpartum infection. The incidence of postpartum endometritis after spontaneous delivery is 1–3%, increasing up to 27% after operative delivery via Cesarean section [20].

Among women who received antibiotic prophylaxis, the incidence of postpartum endometritis is approximately 7.0% in case of Cesarean section performed after the onset of labor and 1.5% in case of elective surgery [49]. In the absence of antibiotic prophylaxis, the incidence of postpartum endometritis is approximately 18% and 4%, respectively [49].

The incidence of peritonitis after Cesarean section ranges from 0.1 to 1.5% in various hospitals [34].

[1] Maternal mortality in the Russian Federation in 2018. Methodological Letter of the Russian Ministry of Health dated September 18, 2019, No. 15-4/i/2-8714.

[2] https://minzdrav.gov.ru/ministry/61/22/stranitsa-979/statisticheskie-i-informatsionnye-materialy/statisticheskiy-sbornik-2018-god

1.4 Features of Coding the Disease or Condition

O85 Puerperal sepsis.

O86.0 Infection of surgical obstetric wound.

O86.1 Other puerperal genital tract infections.

O86.4 Pyrexia of unknown origin following delivery.

O86.8 Other specified puerperal infections.

O88.3 Obstetric pylephlebitic and septic embolism.

O90.0 Disruption of Cesarean section wound.

O90.1 Disruption of perineal obstetric wound.

1.5 Classification of the disease or condition

Classification of SSI [50][1]:

1. superficial surgical site infection (involving skin and subcutaneous tissue);

2. deep surgical site infection (involving muscles and fascia);

3. organ/space surgical site infection.

Classification of postpartum endometritis:

1. postpartum endometritis after spontaneous delivery;

2. postpartum endometritis after Cesarean section.

Classification of peritonitis [2]:

Currently, the classification of peritonitis proposed by V.S. Saveliev et al. and approved at the 11th Congress of Surgeons of Russia in 2011 is generally accepted in the Russian Federation.

1. Main diagnosis.

2. Character of development.

2.1. Primary.

2.1.1. Spontaneous peritonitis in children.

2.1.2. Spontaneous peritonitis in adults.

2.1.3. Peritonitis associated with specific diseases (tuberculosis, syphilis, gonorrhea).

2.2. Secondary.

2.3. Tertiary.

3. Extent.

3.1. Local (involving one or two anatomical regions).

3.1.1. Localized (infiltrate, abscess).

3.1.2. Non-localized.

3.2. Generalized.

3.2.1. Diffuse (from three to five anatomical regions or within a single floor of the abdominal cavity).

3.2.2. Generalised / peritonitis (more than five anatomical regions or two floors of the abdominal cavity).

4. Exudate and its admixtures.

4.1. Character of exudate: serous, fibrinous, purulent, hemorrhagic (and combinations thereof).

4.2. Admixtures: intestinal contents, bile, urine, blood.

5. Severity of the condition depending on the severity of systemic inflammatory response and multiorgan dysfunction (if possible, scored using standard scales).

6. Complications.

6.1. Intra-abdominal: omentitis, unformed intestinal fistulas, parenchymal organ abscesses, stress-induced GI lesions.

6.2. Anterior abdominal wall and retroperitoneal tissue: surgical wound suppuration, abdominal wall phlegmon, retroperitoneal phlegmon, evisceration.

6.3. Extra-abdominal: deep vein thrombosis, pulmonary embolism, pneumonia, pleurisy, mediastinitis.

According to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3, 2016), two conditions are currently distinguished [3] [51]:

• Sepsis.

• Septic shock.

An appropriate specification can be added to the main form depending on the infectious agent, the site of the primary focus, and the pattern of multiorgan failure.

The term "severe sepsis" is redundant and is no longer used.

[1] http://www.cdc.gov/nhsn/PDFs/pscManual/9pscSSIcurrent.pdf

[2] Abdominal surgical infection. Russian national guidelines / Edited by Academician of the RAS B.R. Gelfand, Academician of the RAS A.I. Kirienko, Professor N.N. Khachatryan. M.: Moscow Information Agency, 2018. 164 p.

[3] Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021.

1.6 Clinical presentation of the disease or condition

Classic signs of SSI include hyperemia, local hyperthermia, tissue edema, pain syndrome, decreased wound repair, appearance of purulent discharge, and development of an unpleasant odor [52].

Hidden signs of SSI may include excessive granulation tissue growth, presence of abnormal easily bleeding granulations, increase in wound surface area, and increase in pain syndrome [52–55].

With the spread of local infection, an increase in the area of hyperemia, wound edge dehiscence, and lymphadenitis may be observed. Systemic signs are nonspecific and manifest as general weakness and loss of appetite [13].

Main symptoms of postpartum endometritis:

• Febrile body temperature (>38ºC).

• Pelvic pain or uterine tenderness upon palpation.

• Malodorous or purulent vaginal discharge.

• Uterine subinvolution.

Additional symptoms of postpartum endometritis:

• Moderate vaginal bleeding.

• Nonspecific symptoms: fatigue, chills, decreased appetite, headache [19,55].

Clinical characteristics of the peritonitis phases:

• Reactive phase (duration 24 hours).

• Toxic phase (duration 24–72 hours).

• Terminal phase (duration over 7 hours).

The clinical presentation of obstetric peritonitis typically features early onset (on days 1–2 postoperative), hyperthermia (body temperature of 39.0°C and above), pronounced tachycardia, and intestinal paresis.

Depending on the timing in the postoperative period, paralytic ileus develops by the end of day 2; from days 3–4 postoperatively, there is an increase in signs of intoxication, peritoneal exudation, and intestinal transudation; on days 4–9, peritonitis develops against the background of endometritis and uterine suture failure, accompanied by profuse purulent vaginal discharge and leakage of uterine contents into the peritoneal cavity [34,56].

Clinical signs of postpartum sepsis:

• Fever, chills.

• Hypothermia.

• Generalized maculopapular rash.

• Scleral injection.

• Tachycardia (over 90 beats per minute).

• Tachypnea.

• Hypotension.

• Oliguria.

• Fatigue, decreased appetite.

• Altered mental status.

• Diarrhea, vomiting, abdominal pain.

• Signs of SSSTI.

• Uterine subinvolution.

• Pathological, malodorous vaginal discharge.

• Symptoms of urinary tract infection.

• Lack of adequate physiological response to treatment [36, 39, 61].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Diagnostic criteria for SSSTI[1]:

• purulent wound discharge;

• elevated body temperature >38°C;

• localized pain, edema, hyperemia, local hyperthermia, and induration in the area of the postoperative wound.

Diagnostic criteria for postpartum endometritis[2]:

• fever (>38°C);

• uterine tenderness;

• pelvic and parametrial pain;

• purulent lochia;

• leukocytosis according to the complete blood count.

Diagnostic criteria for obstetric peritonitis[3].

The reactive phase is characterized by:

• intense pain syndrome, defensive tension of the anterior abdominal wall muscles;

• vomiting, agitation, tachycardia (100–120 bpm), hypertension, tachypnea (24–28 breaths per minute);

• fever up to 38ºC.

• moderate leukocytosis with a left shift in the leukocyte formula.

The toxic phase is characterized by:

• predominance of severe systemic intoxication signs;

• tachycardia (120 bpm and above), moderate hypotension, vomiting with stagnant contents;

• hectic fever pattern;

• high leukocytosis, toxic granulation of neutrophils, left shift of the formula;

• diffuse pain without clear localization.

The terminal phase is characterized by:

• progression of peritoneal sepsis.

Abdominal sepsis is diagnosed in the presence of infection and organ dysfunction. In the early stages of hospitalization, organ dysfunction is diagnosed when the qSOFA score is >2 points [58].

Criteria for postpartum sepsis[51]:

• confirmed infection;

• organ dysfunction (a score of two or more points on the SOFA scale, see below and in Appendix G4);

Criteria for septic shock:

• persistent arterial hypotension requiring vasopressor therapy to maintain a mean arterial pressure ≥65 mmHg;

• blood lactate level >2 mmol/L despite adequate fluid resuscitation.

[1] http://www.cdc.gov/nhsn/PDFs/pscManual/9pscSSIcurrent.pdf

[2] WHO Recommendations for Prevention and Treatment of Maternal Peripartum Infections. Geneva: World Health Organization; 2015.

[3] Abdominal surgical infection: Russian national guidelines. Ed. by Academician of the RAS B.R. Gelfand, Academician of the RAS A.I. Kirienko, Professor N.N. Khachatryan. Moscow: Moscow Information Agency, 2018. 164 p.

2.1 Complaints and Anamnesis

Comments. When taking the medical history, special attention should be paid to the following factors (see also section 1.2 Etiology and Pathogenesis):

- previous purulent-septic complications, especially those associated with pregnancy, childbirth, and gynecological diseases;

- presence of a focus of chronic or acute infection;

- presence of immunodeficiency states, as well as conditions requiring immunosuppressive therapy;

- presence of carbohydrate metabolism disorders (impaired glucose tolerance, diabetes mellitus), obesity;

- presence of bad habits;

- invasive procedures or surgical interventions during pregnancy;

- history of prolonged antibacterial drug use;

- prolonged hospitalization (more than seven days);

- anamnestic data on the colonization of the lower genital tract by such bacteria as Streptococcus agalactiae, Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Gardnerella vaginalis.

When assessing complaints, special attention should be paid to:

- dizziness,

- disorientation,

- weakness,

- dyspnea,

- pain and discomfort of various localization,

- sweating,

- appearance of skin rash,

- vaginal discharge of altered color or odor,

- fever, chills,

- palpitations,

- decreased urine output,

- loose stools.

2.2 Physical Examination

• To ensure the timely detection of postpartum infectious complications and assessment of hemodynamic status, it is recommended to monitor the patient's condition in the postpartum period, including [64]:

- pulse rate measurement;

- general thermometry;

- respiratory rate measurement;

- blood pressure measurement in peripheral arteries [59,64,65,66].

GCR BLoE 3Level of Evidence B (Level of Confidence of Evidence – 3)

Comments. Palpation reveals tenderness in all abdominal regions, which may be more pronounced in the projection of the pathological process. The main peritoneal signs are: Shchetkin-Blumberg sign, Mendel's sign, Voskresensky's sign, and Bernstein's sign.

- at the prehospital stage and outside the intensive care unit [51,71–73]:

• quick Sequential Organ Failure Assessment qSOFA (Appendix G1) [51];

• Systemic Inflammatory Response Syndrome (SIRS) criteria (Appendix G2) [74];

• Modified Early Obstetric Warning Score (MEOWS) (Appendix G3) [75,76];

Strong recommendation grade BModerate quality of evidence 3 (Level of recommendation evidence – B, level of data certainty – 3).

- in the ICU, the SOFA scale (Appendix G4) [51].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: A 2018 systematic review and meta-analysis, which included 10 studies and 229,480 patients, showed that the SIRS score was significantly superior to qSOFA in diagnosing sepsis, while qSOFA was slightly better than SIRS in predicting in-hospital mortality [71]. Despite the fact that the qSOFA scale facilitates the rapid identification of patients who are at high risk of adverse outcomes and require escalation of therapy, its preferential use compared to other scales (SIRS or MEWS) for organ dysfunction screening is not advisable [71]. It must be remembered that SIRS criteria often coincide with normal physiological parameters during pregnancy and the early postpartum period [77]. In clinical practice, to assess organ dysfunction in pregnant and postpartum women, the Sepsis in Obstetrics Score (SOS) has also become widespread; it is a modification of generally accepted scales and takes into account physiological changes during pregnancy, but data on its effectiveness are currently insufficient, and further studies are needed to evaluate the efficacy of this scale [78,79].

2.3 Laboratory Diagnostics

Comments: Biological material collection should be performed before prescribing antibiotic therapy in all cases, unless this leads to a delay in antimicrobial therapy (no more than 45 minutes) [73,83]. Routine microbiological testing should always include at least 2 blood samples (aerobic and anaerobic media in each) [84]. Identification of the infectious agent in sepsis is a challenging task due to the wide variety of pathogens, many of which are part of the normal human microflora. In order to accelerate pathogen identification, detect non-culturable microorganisms, and identify antibiotic resistance factors, molecular biological analysis methods—hybridization methods, polymerase chain reaction, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF)—are recommended as additional to the microbiological (culture) examination of purulent discharge for aerobic and facultative anaerobic microorganisms and other biological material [85–89]. The advantages of these methods are reduced analysis time, the possibility of early detection of non-culturable microorganisms, and the identification of antibiotic resistance factors [89]. Currently, these diagnostic methods have limited availability, but can be recommended as additional tests when laboratories are equipped accordingly.

Comments; Lactic acid (lactate) levels are not a direct indicator of tissue perfusion [96]. An increase in blood lactate levels may indicate tissue hypoxia, increased aerobic glycolysis, and other factors. Regardless of the cause, elevated lactate levels are associated with the most adverse outcomes [97]. If the initial lactate level is >2 mmol/L, it is advisable to repeat testing every 2–4 hours until normalization [90].

Comments: Despite its low specificity, C-reactive protein (CRP) testing has high sensitivity in the early stages of sepsis [98]. A study revealed that in postpartum women on the third postpartum day, the sensitivity of a CRP level above 60 mg/L for postpartum endometritis was 79% (95% CI 68–86) and the specificity was 93% (95% CI 85–98) [100]. The results of several studies have also shown that CRP levels are elevated during the first two days after delivery, which can complicate the assessment of infection [101,103,104]. If available, blood presepsin testing is recommended for patients with suspected sepsis or septic shock, as well as for confirmed cases, to monitor the patient's condition and adjust therapy in a timely manner [105–107]. According to a meta-analysis including 9 publications and 1561 patients, presepsin can serve as an effective diagnostic marker and predictor of mortality in sepsis (AUC was 0.77 (95% CI 0.73–0.81) with a pooled prognostic sensitivity (SEN) and specificity (SPE) of 0.83 (95% CI 0.72–0.90) and 0.69 (95% CI 0.63–0.74), respectively) [107].

• In cases of suspected sepsis or septic shock, blood procalcitonin testing is not recommended to guide the initiation of antibacterial therapy compared to clinical evaluation alone [73,108–110].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments. Blood procalcitonin testing is recommended only in conjunction with clinical evaluation to determine the duration of antibacterial therapy in patients with sepsis or septic shock, provided there is adequate control of the source of sepsis and/or septic shock [73,108–110].

2.4 Instrumental Diagnostics

Comments: a decrease in SpO₂ below 90% corresponds to a decrease in PaO₂ below 60 mmHg according to the oxyhemoglobin dissociation curve [124].

Comments. The sonographic picture in postpartum endometritis is highly polymorphic, which precludes recommending this method as a diagnostic tool for postpartum endometritis [125,130,131]. However, pelvic ultrasound is of clinical importance for detecting retained placental tissue and pelvic abscesses [95, 97].

Comments. If abdominal ultrasound findings are inconclusive, an abdominal CT scan is recommended [135–137].

Comments. The sensitivity of chest radiography for ARDS in the presence of bilateral infiltrates (the hallmark symptom of ARDS) is approximately 75%, and specificity is 70% [104, 105].

Comments: Currently, there are no large randomized trials comparing invasive blood pressure monitoring with non-invasive methods. Considering the low complication rate and presumably higher measurement accuracy, the benefits of arterial catheters likely outweigh the risks. However, potentially limited resources in certain countries and the lack of high-quality studies on this technique must be taken into account. Therefore, the expert panel issued a weak recommendation in favor of arterial catheter use. To minimize the risk of complications, arterial catheters should be promptly removed when continuous hemodynamic monitoring is no longer required.

2.5 Other Procedures

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1. Treatment of SSI

Comments: Surgical debridement of purulent-necrotic foci is performed with adequate drainage and removal of necrotic tissue to prevent further spread of infection. In addition, the pathways of infection spread at the level of subcutaneous adipose tissue, fasciae, tendons, and interfascial spaces must be controlled [152]. Secondary suturing after surgical wound debridement is recommended in patients with HCAIs, as it is associated with faster wound repair compared to healing by secondary intention [155].

Comments: Possible empirical antibacterial regimens (antibacterial therapy may subsequently be modified based on microbiological culture and susceptibility results) [152]:

- oral administration – Amoxicillin + [Clavulanic Acid]** 875/125 mg every 12 h;

- ciprofloxacin** 500 mg every 12 h + Metronidazole** 500 mg every 8 h;

3.2. Treatment of postpartum endometritis

Comments. A 2015 meta-analysis involving 40 randomized trials and 4240 patients demonstrated that combination therapy including intravenous clindamycin** with gentamicin** showed higher efficacy in the treatment of postpartum endometritis compared to other antimicrobial drugs or combinations. None of the studies reported maternal mortality or differences in the incidence of severe complications across various antibiotic groups [20].

Possible empirical antibacterial regimens (antibacterial therapy may subsequently be modified based on microbiological culture and susceptibility results):

Oral:

- Amoxicillin** 500 mg every 8 h + Metronidazole** 500 mg every 8 h [159];

- Amoxicillin + [Clavulanic Acid]** 875 mg + 125 mg every 12 h [159];

Intravenous:

- Clindamycin** 900 mg every 8 h intravenously + # Gentamicin** 5 mg/kg (for adults with normal renal function) intravenously every 24 h [20].

Carbapenems may be used upon receipt of microbiological test results identifying multiresistant opportunistic pathogens or in the absence of clinical efficacy within 48–72 hours.

3.3 Treatment of obstetric peritonitis

Comments. The key factors for effective treatment of obstetric peritonitis are timely diagnosis, adequate resuscitation measures, early initiation of antimicrobial therapy, source control and debridement of the infection, as well as reassessment of the clinical response and appropriate adjustment of the management strategy [132].

The Antimicrobial Testing Leadership and Surveillance (SMART) study provides in vitro data on the antimicrobial susceptibility of gram-negative bacteria in intra-abdominal infections since 2002 [160]. Results of local resistance studies and pharmacoepidemiology of anti-infective drugs help ensure adequate antimicrobial therapy [160, 161]. The WHO Expert Committee recommends piperacillin + [tazobactam] as the first-line therapy for complicated intra-abdominal infections, and meropenem** as the second-line therapy[1].

3.4 Treatment of sepsis and septic shock

It should be noted that today, studies on obstetric sepsis are practically nonexistent for ethical reasons, and the principles of obstetric sepsis therapy are largely extrapolated from the general population.

Early goal-directed therapy improves survival in patients with septic shock. Emergency treatment within the first 6 hours of resuscitation can reduce 28-day mortality.

A key aspect of managing patients with sepsis is the urgency of the medical care provided. Early detection and prompt treatment improve patient outcomes [61, 89, 107–110].

3.4.1 Antibacterial therapy

• If septic shock is suspected or there is a high probability of sepsis in a patient, it is recommended to initiate empirical systemic antibacterial therapy within 1 hour [72, 73, 165, 166].

GCR BLoE 3Level of Evidence B (Level of Confidence of Evidence – 3)

Comments. Timely early treatment with high doses of intravenous broad-spectrum antibiotics (systemic antibacterial drugs) increases the likelihood of a favorable outcome. Delaying adequate antimicrobial therapy after the onset of clinical symptoms of sepsis is associated with increased mortality [166–169], and every hour of delay in adequate antimicrobial therapy reduces patient survival [110, 118]. When choosing empirical antimicrobial therapy, it is extremely important to take local data into account. The results of local resistance studies and pharmacoepidemiology of anti-infective agents make it possible to provide adequate antimicrobial therapy [160, 161].

In 2019, the WHO launched a global campaign urging governments to implement the developed AWaRe antibiotic classification, which is a database of antibacterial drugs divided into three groups: Access, WAtch, and REserve, aimed at combating antimicrobial resistance[2]. A new target was adopted based on the AWaRe classification, which sets the objective of ensuring that at least 60% of antibiotics used at the national level belong to the Access group[3]. Where available, these data should be taken into account when choosing antimicrobial therapy.

Comments. If the development of sepsis is associated with the localization of the infection focus in the uterus, the choice of possible antibacterial therapy regimens is based on the guidelines for the treatment of postpartum endometritis.

Adjustment of antibacterial therapy should be based on the results of culture studies 48–72 hours after the start of treatment if there is no improvement in clinical and laboratory parameters indicating positive disease dynamics and/or pathogen resistance to the ongoing therapy [170].

Comments. De-escalation antibacterial therapy does not increase mortality in patients with sepsis and/or septic shock [171–174], but provides an opportunity to limit the use of broad-spectrum antibiotics, which is important in combating the development of microbial resistance to antibacterial drugs. Subsequently, patients' antibacterial therapy should be adjusted based on microbiological and susceptibility test results, if available.

3.4.2 Infusion therapy

Comment. If signs of right heart overload increase, a reduction in the rate of infusion therapy and individual selection of the administered infusion volume are recommended [175].

Comments. CVP, systolic blood pressure, and heart rate are less informative indicators of volume status. More indicative are an increase in cardiac output in response to changes in intrathoracic pressure or an increase in stroke volume in response to 1–3 ml/kg fluid boluses. If echocardiography is unavailable, a 45° passive leg raise test for 60–90 seconds can be performed with an increase in pulse pressure by more than 15% [176–178]. There is insufficient data on the benefits of a liberal fluid strategy compared to a restrictive one in sepsis and septic shock within the first 24 hours regarding mortality reduction [179].

Comments. A meta-analysis of 14 RCTs evaluating the efficacy of infusion therapy for patients with sepsis and septic shock showed that the use of balanced crystalloids compared to isotonic sodium chloride solution was associated with reduced mortality in patients with septic shock [180]. In the 2018 cluster randomized SMART trial, 30-day mortality in critically ill patients was lower in the balanced crystalloid solutions group compared to the saline group (OR 0.90; 95% CI = 0.67–0.94) [181] (Appendix A3).

Comments: The use of human albumin** (B05AA – Blood substitutes and plasma protein fractions) as infusion therapy is safe [182] and effective in reducing mortality in patients with sepsis and/or septic shock [138, 139].

Comments: Hydroxyethyl starch preparations** are contraindicated in sepsis and septic shock as they are associated with a high risk of death [180]. In addition, the use of hydroxyethyl starch** is associated with an increased need for renal replacement therapy in patients with sepsis and septic shock [185].

3.4.3 Vasopressor therapy

• In patients with septic shock, recommended is the use of norepinephrine** (C01CA - Adrenergic and dopaminergic agents) as the first-line vasopressor therapy to achieve a target mean arterial pressure of more than 65 mmHg [186, 187].

GCR ALEL 1Grade of Recommendations A (Level of Evidence – 1)

Comments. Immediate restoration of perfusion pressure in vital organs is one of the key resuscitation goals in patients with sepsis and/or septic shock. The use of norepinephrine** is associated with a lower mortality rate and a lower risk of arrhythmias in patients with septic shock compared to dopamine** [141, 142].

• To achieve a target mean arterial pressure of more than 65 mm Hg when norepinephrine** is insufficiently effective, it is recommended to use a combination of norepinephrine** and epinephrine** in patients with sepsis and/or septic shock [73].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: Studies demonstrate lower mortality rates with norepinephrine** in patients with septic shock compared to dopamine**. In addition, the use of dopamine** more frequently causes cardiac rhythm disturbances in patients with sepsis and/or septic shock compared to norepinephrine** [142, 143].

• In patients with septic shock and persistent tissue hypoperfusion despite adequate fluid resuscitation and vasopressor therapy, or in patients with myocardial dysfunction established on the basis of etCO₂ and echocardiography, it is recommended to add dobutamine** (C01CX: Other cardiotonic agents) to norepinephrine** as inotropic therapy or to use epinephrine** alone [73, 190].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments. Despite the lack of randomized placebo-controlled trials evaluating clinical outcomes, the use of dobutamine** as the drug of choice for inotropic therapy in studies has not shown an increase in mortality in patients with sepsis and/or septic shock. At the same time, inotropic therapy with dobutamine** and routine escalation of the cardiac index to supranormal values does not lead to improved outcomes in patients with sepsis and/or septic shock [145, 146]. Currently, there are no comparative studies on the efficacy of dobutamine** and epinephrine**; according to a network meta-analysis, similar mortality rates were obtained with both the first and second drugs [190].

Comment. A meta-analysis of three RCTs showed that levosimendan** does not reduce mortality in septic shock compared to no inotropic drugs (OR 0.87; 95% CI = 0.59-1.28) [194]. Another meta-analysis based on 7 RCTs showed that levosimendan is not superior to dobutamine in reducing mortality in patients with septic shock (OR 0.80; 95% CI = 0.48-1.33) [193]. Thus, the results of these studies do not allow recommending the routine use of levosimendan** for the treatment of septic shock.

Comments. Intravenous administration of #hydrocortisone** at a dose of no more than 200 mg per day at 50 mg every 6 hours or as a continuous infusion is recommended. Therapy may be initiated when the norepinephrine** dosage is greater than 0.25 mcg/kg/min for at least 4 hours [198, 199]. The use of glucocorticoids in patients with sepsis leads to a reduced risk of death, as well as a significant reduction in the length of stay in the intensive care unit and hospital [202]. Continuous intravenous infusion is recommended to prevent hyperglycemia [202, 203], along with a gradual taper of glucocorticoids after vasopressor therapy is discontinued [197].

3.4.4 Transfusion therapy

• When hemoglobin levels drop below 70 g/L in patients with sepsis and/or septic shock, red blood cell transfusion (B05AX01: Erythrocytes) is recommended [73].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments. Red blood cell transfusion is recommended in the absence of complicating conditions such as myocardial ischemia, severe hypoxemia, or acute bleeding [73]. Choosing a hemoglobin threshold of 90 g/L does not improve 30-day [204] or 90-day survival in patients with sepsis and/or septic shock [205].

• Transfusion of fresh frozen plasma to correct coagulation disorders is not recommended in patients with sepsis and septic shock [73].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments. In the absence of bleeding or planned invasive procedures, fresh frozen plasma transfusion is not recommended [112].

Comment. The use of antithrombin does not reduce mortality in sepsis and

septic shock, but increases the risk of bleeding [209].

3.4.5 Respiratory therapy

• For patients with respiratory failure caused by sepsis (without ARDS), it is recommended to use a low tidal volume compared to high tidal volume ventilation [211] .

GCR ALEL 1Grade of Recommendations A (Level of Evidence – 1)

Comments: There are limited data on ventilation strategies in patients with sepsis-induced respiratory failure who do not meet ARDS criteria. However, sepsis is an independent risk factor for the development of ARDS, and delays in diagnosing ARDS can lead to deferred use of low tidal volumes. Therefore, we suggest using low tidal volume ventilation in all patients with sepsis undergoing mechanical ventilation to avoid inadequate or delayed implementation of this intervention. Furthermore, the use of low tidal volume ventilation prevents the risk of ventilator-induced lung injury in patients with sepsis in whom an ARDS diagnosis was missed.

Comments: Absolute indications for initiating mechanical ventilation include: absence of spontaneous breathing and pathological breathing patterns, upper airway obstruction, PaO₂/FiO₂ ratio less than 200 mmHg, septic shock, hemodynamic instability with the development of life-threatening arrhythmias, persistent tachycardia, and hypotension. The presence of two relative indications constitutes an indication for starting mechanical ventilation: PaO₂/FiO₂ ratio less than 300 mmHg, development of septic encephalopathy and cerebral edema with depressed consciousness and impaired external respiration, hypercapnia or hypocapnia (PaCO₆ less than 25 mmHg), tachypnea greater than 40 breaths/min and progressive increase in minute ventilation, decrease in vital capacity less than 10 mL/kg of body weight, decrease in compliance less than 60 mL/cmH2O, increase in airway resistance greater than 15 cmH2O/L/s, patient fatigue, and recruitment of accessory respiratory muscles [212–214].

• During mechanical ventilation in patients with sepsis and septic shock, it is recommended to use a low tidal volume strategy of 6 mL/kg of ideal body weight [73].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments. The use of tidal volumes up to 6 mL/kg leads to a decrease in mortality and the incidence of ventilator-associated pneumonia and atelectasis compared to higher tidal volumes [211], whereas tidal volumes greater than 10 mL/kg of ideal body weight lead to increased organ dysfunction and prolonged respiratory support [215]. An analysis of 10 RCTs involving patients with ARDS demonstrated a dose- and time-dependent increase in mortality when oxygenation targets exceeded 6 mL/kg across all severities of ARDS [216].

Comments: Studies comparing the use of high versus low PEEP levels have demonstrated a reduction in mortality with high PEEP levels [219,220], reaching 10–15 mbar [221,222].

3.4.6 Prevention of complications

Comments: Risk factors for candidiasis include: presence of Candida species in multiple loci [223], neutropenia [224], immunosuppression [225], severity of condition (high APACHE II score) [226], prolonged stay in the intensive care unit [227], presence of a central venous catheter or other intravascular devices, substance abuse, total parenteral nutrition, broad-spectrum antibiotic therapy [228], acute kidney injury, and hemodialysis [229]. The initiation of empirical antifungal therapy depends on the type and number of risk factors for fungal infection in the patient, as well as local epidemiological data [73].

Comments: Hyperglycemia (>180 mg/dL), hypoglycemia, and increased glucose variability are associated with high mortality in critically ill patients [231]. A 2017 meta-analysis showed that glucose levels of <110 and 110–144 mg/dL are associated with an increased risk of hypoglycemia compared to levels of 144–180 and >180 mg/dL. At the same time, no significant difference in the risk of hypoglycemia was found between glycemic levels of 144–180 and >180 mg/dL [235]. Nevertheless, it is currently recommended to initiate insulin administration (ATC A10A Insulins and analogues) at glucose levels >180 mg/dL due to the increased risk of hypoglycemia [73].

Comments: A Cochrane review demonstrated that combined prophylaxis is more effective than any single method alone; however, the methodological limitations of this study preclude grading this recommendation as strong [236]. When comparing unfractionated heparin preparations (B01AB — Heparin group) and low-molecular-weight heparin (LMWH) preparations (B01AB — Heparin group), another Cochrane review showed that LMWHs are more effective in reducing thromboembolic complications [237].

Comments: ICU patients are at high risk for thromboembolic complications, with deep vein thrombosis rates reaching up to 10% and pulmonary embolism rates reaching 2–4% [236,237,241].

3.4.7 Other methods

• Following successful initial resuscitation, it is recommended to sanitize the source of sepsis and/or septic shock within no more than 12 hours after diagnosis [242–245].

GCR BLEL 3Grade of Recommendation B (Level of Evidence – 3)

• In patients with sepsis and acute kidney injury, it is recommended to use continuous or intermittent renal replacement therapy [250,251].

GCR BLoE 1Grade of Recommendation B (Level of Evidence – 1)

• The use of renal replacement therapy is not recommended for rising creatinine levels or oliguria in the absence of other clear indications for dialysis [252–254].

Strong recommendation grade CLOE 2Level of Evidence C (Level of Evidence — 2)

• The routine use of polyclonal and monoclonal immunoglobulins is not recommended in the treatment of patients with sepsis and/or septic shock due to insufficient evidence of efficacy, and further research is needed [255].

GCR BLoE 1Grade of Recommendation B (Level of Evidence – 1)

Comments: The efficacy of polyclonal and monoclonal immunoglobulin therapy in sepsis remains controversial and requires confirmation in larger studies [255].

• The routine use of high-volume hemofiltration is not recommended in the treatment of patients with sepsis and/or septic shock due to the low quality of evidence from conducted studies; further research is required to evaluate treatment efficacy [256].

GCR BLoE 1Grade of Recommendation B (Level of Evidence – 1)

• The routine use of plasmapheresis is not recommended in the treatment of patients with sepsis and/or septic shock [257–260].

GCR BLoE 1Grade of Recommendation B (Level of Evidence – 1)

Comments: Routine therapeutic plasma exchange is not recommended for the treatment of patients with sepsis and/or septic shock; however, this treatment method may be considered if specialists and appropriate facilities for extracorporeal techniques are available [261]. Extracorporeal blood purification is considered a promising strategy for eliminating inflammatory mediators and microbial toxins; nevertheless, randomized controlled trials have shown that the risk-benefit ratio for most techniques remains uncertain, with the exception of selective LPS adsorption procedures using immobilized polymyxin B columns and therapeutic plasma exchange [258,262]. A retrospective observational study in adult patients with septic shock and multiple organ dysfunction demonstrated an improvement in 28-day survival with adjunctive therapeutic plasma exchange compared to standard care. Hemodynamics, organ dysfunction, and fluid balance improved with adjunctive therapeutic plasma exchange, and the length of hospital stay among survivors was prolonged [262]. Data from a randomized controlled trial showed that therapeutic plasma exchange in a subgroup of patients with septic shock resulted in rapid hemodynamic improvement [258]. Further multicenter randomized trials with adequate statistical power are required to determine the treatment strategy in patients with sepsis and septic shock.

Comments: At the same time, recent meta-analyses have shown that proton pump inhibitors (A02BC Proton pump inhibitors) are more effective in reducing the incidence of clinically significant gastrointestinal bleeding compared to H₂-receptor antagonists (A02BA — H2-receptor antagonists) [264–266].

[1] https://apps.who.int/iris/handle/10665/331990

[2] https://aware.essentialmeds.org/groups

[3] https://apps.who.int/iris/handle/10665/331990

4. Medical Rehabilitation and Sanatorium-Resort Treatment

• Currently, standardized approaches to the rehabilitation of patients with postpartum infectious complications have not been developed. It is recommended to follow general rehabilitation guidelines for patients recovering from infectious diseases and sepsis [267–269].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

5. Prevention and Dispensary Observation

Currently, given the rise of antimicrobial resistance, measures aimed at preventing purulent-septic complications in the postpartum period must be intensified.

• In cases of third- and fourth-degree perineal lacerations, it is recommended to administer antibiotic prophylaxis to prevent purulent-septic complications in the postpartum period [271].

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)

• During manual removal of the placenta and extraction of the afterbirth, antibiotic prophylaxis is recommended to prevent purulent-septic complications in the postpartum period [67].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: see also Order of the Russian Ministry of Health No. 1108n dated November 29, 2021, "On Approval of the Procedure for Conducting Preventive Measures, Detecting and Registering Cases of Healthcare-Associated Infections in a Medical Organization, and the Nomenclature of Healthcare-Associated Infections Subject to Detection and Registration in a Medical Organization".

6. Organization of Medical Care

Sepsis and septic shock are conditions that require resuscitation and intensive care measures for patients, as well as consultation and ongoing patient monitoring at an obstetric remote consultation center.

Emergency and urgent medical care is provided in two stages:

1. outside a medical organization — provided by an emergency cardiology/anesthesiology-resuscitation team for emergency and urgent care to women during pregnancy, childbirth, the postpartum period, and with gynecological pathologies, consisting of anesthesiologists-resuscitators skilled in urgent diagnostics, resuscitation, and intensive care in obstetrics and gynecology; obstetrician-gynecologists proficient in the full range of surgical interventions in obstetrics and gynecology; and nurse anesthetists trained in emergency care skills in neonatology and obstetrics-gynecology, or, in the absence of a specialized resuscitation team, by general emergency teams;

2. in inpatient settings — provided in anesthesiology-resuscitation departments of medical organizations.

The grounds for transferring postpartum women to a specialized department for further monitoring and treatment are:

1. sustained restoration of hemodynamics and spontaneous respiration;

2. correction of metabolic disorders;

3. stabilization of vital functions.

7. Additional Information

Postpartum infectious complications are typically healthcare-associated infections (HAIs). HAIs in the postpartum period can be caused by either exogenous or endogenous infection.

The main forms of HAIs in the postpartum period are:

1. Purulent-septic infections of puerperas (PSI of puerperas): sepsis, childbirth-related nipple and breast infections, acute peritonitis, surgical obstetric wound infection, dehiscence of cesarean section sutures, perineal suture dehiscence, postpartum urinary tract infections, and respiratory tract infections complicating labor and the postpartum period.

2. Surgical site infections (SSIs).

Every case of HAI must be recorded in the register of infectious diseases at the place of detection and the place of patient infection within medical organizations, as well as in territorial bodies authorized to exercise federal state sanitary and epidemiological supervision. All HAI cases are recorded at the location where the patient was infected.

If an HAI is detected after discharge or transfer of the patient to another hospital, the medical organization that detected the HAI must transmit information to the territorial bodies authorized to exercise federal state sanitary and epidemiological supervision, which within 12 hours shall transmit information on the registered HAIs to the medical organization at the presumed site of infection.

Criteria for Evaluating the Quality of Medical Care

Quality assessment criteria for medical care. Surgical site infection.

Quality assessment criteria for medical care. Postpartum endometritis.

Quality assessment criteria for medical care. Obstetric peritonitis.

Quality assessment criteria for medical care. Postpartum sepsis. Septic shock.

References

Appendix A1. Working Group Composition

1. Natalia E. Kan – MD, PhD, Professor, Deputy Director for Research, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). There is no conflict of interest.

2. Viktor L. Tyutyunnik – MD, PhD, Professor, Leading Researcher, Center for Scientific and Clinical Research, Department of Scientific Activity Organization, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). There is no conflict of interest.

3. Zarine V. Khachatryan – PhD, Obstetrician-Gynecologist, European Medical Center JSC (Moscow). There is no conflict of interest.

4. Sergey G. Ababkov – Head of the Department of Anesthesiology and Intensive Care, Ekaterinburg Clinical Perinatal Center (Ekaterinburg). There is no conflict of interest.

5. Elrad Yu. Amiraslanov – PhD, Head of the Obstetric Department, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). There is no conflict of interest.

6. Natalia V. Artymuk – MD, PhD, Professor, Head of the Department of Obstetrics and Gynecology named after Professor G.A. Ushakova, Kemerovo State Medical University of the Russian Ministry of Health, Chief freelance obstetrician of the Russian Ministry of Health, Chief freelance gynecologist of the Russian Ministry of Health, Chief freelance specialist in women's reproductive health of the Russian Ministry of Health in the Siberian Federal District (Kemerovo). There is no conflict of interest.

7. Anastasia N. Akhmatova – PhD, Associate Professor at the Department of Obstetrics and Gynecology with a Course in Perinatology, Peoples' Friendship University of Russia, Honored Worker of Science of the Russian Federation (Moscow). There is no conflict of interest.

8. Igor I. Baranov – MD, PhD, Professor, Head of the Department of Scientific and Educational Programs, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). There is no conflict of interest.

9. Tatiana E. Belokrinitskaya – MD, PhD, Professor, Head of the Department of Obstetrics and Gynecology, Faculty of Advanced Training and Professional Retraining of Physicians, Chita State Medical Academy of the Russian Ministry of Health, Honored Doctor of the Russian Federation, Chief freelance obstetrician of the Russian Ministry of Health, Chief freelance gynecologist of the Russian Ministry of Health, Chief freelance specialist in women's reproductive health of the Russian Ministry of Health in the Far Eastern Federal District (Chita). There is no conflict of interest.

10. Akim S. Bykov – PhD, Anesthesiologist-Intensivist, Ekaterinburg Clinical Perinatal Center (Ekaterinburg). There is no conflict of interest.

11. Kirill A. Desyatnik – Obstetrician-Gynecologist, Organizational and Methodological Department, Ekaterinburg Clinical Perinatal Center (Ekaterinburg). There is no conflict of interest.

12. Natalia V. Dolgushina – MD, PhD, Professor, Deputy Director – Head of the Department of Scientific Activity Organization, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). There is no conflict of interest.

13. Alla A. Ignatyeva – PhD, Head of the 2nd Obstetric Physiological Department, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). There is no conflict of interest.

14. Vladimir A. Klimov – PhD, Head of the Medical Care Organization and Information Service , National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). There is no conflict of interest.

15. Aleksandr V. Kulikov – MD, PhD, Professor, Vice-President of the Association of Obstetric Anesthesiologists and Intensivists (AAR), Board Member of the Federation of Anesthesiologists and Reanimatologists (FAR), Chairman of the FAR Committee on Anesthesia and Intensive Care in Obstetrics and Gynecology, Professor at the Department of Obstetrics, Gynecology and Transfusiology, Ural State Medical University of the Russian Ministry of Health, Ekaterinburg. There is no conflict of interest.

16. Sergey V. Martirosyan – PhD, Chief Medical Officer, Ekaterinburg Clinical Perinatal Center, Associate Professor at the Department of Obstetrics and Gynecology, Faculty of Medicine and Prophylaxis, Ural State Medical University (Ekaterinburg). There is no conflict of interest.

17. Anastasia V. Nikolaeva – PhD, Chief Medical Officer, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). There is no conflict of interest.

18. Olga V. Perevozkina – PhD, Head of the Organizational and Methodological Department, Ekaterinburg Clinical Perinatal Center (Ekaterinburg). There is no conflict of interest.

19. Tatiana V. Priputnevich – Corresponding Member of the RAS, MD, PhD, Director of the Institute of Microbiology, Antimicrobial Therapy and Epidemiology, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health, Professor at the Department of Microbiology and Virology, Pediatric Faculty, Pirogov Russian National Research Medical University, Chief freelance specialist in medical microbiology of the Russian Ministry of Health (Moscow). There is no conflict of interest.

20. Denis N. Protsenko – PhD, Associate Professor, Head of the Department of Anesthesiology and Reanimatology, Pirogov Russian National Research Medical University of the Russian Ministry of Health, Chief Medical Officer of City Clinical Hospital No. 40 of the Moscow Healthcare Department, Chief freelance anesthesiologist-intensivist of the Moscow Healthcare Department, Presidium Member of the Association of Obstetric Anesthesiologists and Intensivists, Moscow. There is no conflict of interest.

21. Ivan A. Pryalukhin – PhD, Head of the Project Methodology Division, Department of Project Activity Organization, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). There is no conflict of interest.

22. Aleksey V. Pyregov – MD, PhD, Professor, Deputy Chief Medical Officer for Anesthesiology and Intensive Care, Moscow Regional Perinatal Center, Chief freelance specialist in obstetric anesthesiology and reanimatology of the Moscow Region Ministry of Health. There is no conflict of interest.

23. Viktor E. Radzinsky – MD, PhD, Professor, Corresponding Member of the RAS, Head of the Department of Obstetrics and Gynecology with a Course in Perinatology, Peoples' Friendship University of Russia, Honored Worker of Science of the Russian Federation (Moscow). There is no conflict of interest.

24. Oleg V. Rogachevsky – MD, PhD, Transfusiologist, Obstetrician-Gynecologist, Head of the Department of Extracorporeal Treatment and Detoxification, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). There is no conflict of interest.

25. Ronenson Alexander Mikhailovich – Candidate of Medical Sciences, Chief Freelance Anesthesiologist-Resuscitator in Obstetrics and Gynecology of the Ministry of Health of Tver Region, Head of the Department of Anesthesiology and Intensive Care at the Tver Regional Clinical Perinatal Center named after E.M. Bakunina, Scientific Secretary of the AAR Association, Assistant Professor at the Department of Anesthesiology, Intensive Care and Critical Care Medicine at the Tver State Medical University of the Ministry of Health of the Russian Federation, Tver. No conflict of interest.

26. Serov Vladimir Nikolaevich – Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Honored Scientist of the Russian Federation, President of the Russian Society of Obstetricians and Gynecologists, Chief Researcher at the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of Russia (Moscow). No conflict of interest.

27. Troshin Pavel Vladimirovich – Anesthesiologist-Intensivist, Assistant Professor at the Department of Anesthesiology and Intensive Care, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of Russia (Moscow). No conflict of interest.

28. Fedorova Tatyana Anatolyevna – Doctor of Medical Sciences, Head of the Department of Transfusiology and Hemocorrection, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of Russia (Moscow). No conflict of interest.

29. Shabanova Natalya Evgenyevna – Candidate of Medical Sciences, Associate Professor, Head of the Department of Clinical Pharmacology of Antimicrobial and Immunobiological Drugs, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of Russia (Moscow). No conflict of interest.

30. Sheshko Elena Leonidovna – Candidate of Medical Sciences, Associate Professor, Head of the Department of Project Activity Organization, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of Russia (Moscow). No conflict of interest.

31. Shifman Efim Munevich – Doctor of Medical Sciences, Professor, President of the AAR Association, Vice-President of the FAR, Member of the FAR Presidium, Board Member of the World Society of Intravenous Anesthesia (SIVA), Board Member of the Moscow Scientific Society of Anesthesiologists and Intensivists, Honored Physician of the Republic of Karelia, Professor at the Department of Anesthesiology and Intensive Care of the Faculty of Advanced Medical Training at the Moscow Regional Research Clinical Institute named after M.F. Vladimirsky, Moscow. No conflict of interest.

32. Shmakov Roman Georgievich – Doctor of Medical Sciences, Professor of the Russian Academy of Sciences, Director of the Institute of Obstetrics at the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of Russia (Moscow). Chief Freelance Specialist in Obstetrics of the Ministry of Health of Russia (Moscow). No conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. obstetrician-gynecologists;

2. anesthesiologists-intensivists;

3. students; obstetrics and gynecology residents, postgraduate students; anesthesiology and intensive care residents, postgraduate students;

4. faculty members, researchers.

Table 1. Scale for assessing levels of reliable evidence (LRE) for diagnostic methods (diagnostic interventions)

Table 2. Scale for assessing the levels of evidence (LE) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3. Scale for grading grades of recommendation (GR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their systematic revision — at least once every three years, as well as upon the emergence of new evidence-based medicine data regarding the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

Characteristics of certain crystalloid solutions (B05BB: Solutions affecting the water-electrolyte balance) for infusion therapy

Appendix B. Physician Action Algorithms

Algorithm for diagnosis of sepsis and septic shock

Initial therapy for sepsis/septic shock

Algorithm for determining the tactics of focus sanitation (hysterectomy)

Appendix C. Patient Information

What are postpartum infectious complications?

Postpartum infectious complications are a group of infectious diseases that develop in women in the postpartum period and include surgical site infections, breast infections, postpartum endometritis, obstetric peritonitis, sepsis, and septic shock.

What are the causes of postpartum infectious complications?

Infections are caused by various microorganisms. The development of infection triggers the activation of cellular and humoral components of the immune system, as well as a number of other biological mechanisms that lead to the localization of the infection focus and prevent its spread. These processes are called inflammation.

If your immune system is weak or the infection is particularly severe, it may rapidly spread to other tissues and organs. The generalization of infection leads to the adverse systemic effects of inflammation on the entire body. Inflammation causes tissue damage, reduced blood flow, a dangerous drop in blood pressure, and decreased oxygen delivery to organs and tissues.

What are the symptoms of postpartum infectious complications?

Surgical site infection is characterized by purulent discharge from the postoperative wound, localized pain, swelling, induration around the wound, and elevated local temperature as well as a body temperature above 38ºC.

The main symptom of postpartum endometritis is fever with a body temperature above 38ºC. In addition, chills, pelvic pain, foul-smelling or purulent vaginal discharge, a general feeling of discomfort or malaise, headache, fatigue, and decreased appetite may be observed. As a rule, in most cases, postpartum endometritis is diagnosed within 10 days after delivery.

The initial stage of obstetric peritonitis is characterized by intense abdominal pain, vomiting, increased heart and respiratory rates, and fever with a body temperature above 38ºC.

Early symptoms of sepsis may include: high or low body temperature, chills, rapid heartbeat and breathing. Other symptoms may include: confusion, slurred speech, dizziness, fainting, nausea, vomiting, severe muscle pain, pronounced shortness of breath, decreased urine output, and pallor.

How are postpartum infectious complications treated?

Treatment of surgical site infections is comprehensive and includes both surgical debridement of the postoperative wound area and antibacterial therapy.

Treatment of postpartum endometritis primarily includes antibacterial therapy, as well as additional supportive therapies under the control of clinical and laboratory parameters.

In case of suspected obstetric peritonitis and sepsis, immediate hospitalization in a hospital setting is required first and foremost. Most patients require medical care in an intensive care unit.

Due to vital organ damage, outcomes of sepsis can be extremely unfavorable. However, with early detection and treatment, a full recovery occurs in most cases. Spsis treatment is monitored using clinical and laboratory parameters and includes antibacterial therapy, infusion therapy (intravenous administration of solutions), oxygen therapy, sanitation of the sepsis source, and other comprehensive treatment methods.

How does rehabilitation proceed after postpartum infectious complications?

After discharge home, patients may experience severe fatigue, decreased appetite, muscle mass loss with decreased muscle tone, generalized weakness, brittle nails and teeth, dry and flaking skin, thinning and hair loss, and low mood. To help the body recover, prolonged rest and proper care under the supervision of an obstetrician-gynecologist, general practitioner, physical therapist, and other specialists are necessary.

Some individuals experience depression, anxiety disorders, and social withdrawal after sepsis. Family and friend support, as well as specialist consultations, can help overcome these issues.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1. Quick Sequential Organ Failure Assessment (qSOFA) scale

Russian name: Quick Sequential Organ Failure Assessment qSOFA scale

Original name: quick Sepsis Related Organ Failure Assessment, quickSOFA, qSOFA

Source: Brabrand M., Havshøj U., Graham C. A. Validation of the qSOFA score for identification of septic patients: a retrospective study //European journal of internal medicine. – 2016. – Vol. 36. – P. e35-e36., https://qsofa.org/research.php

Type: rating scale

Purpose: screening assessment for organ dysfunction, identification of patients with suspected infection who are at higher risk of adverse outcomes outside the intensive care unit (ICU)

Content:

Key (interpretation):

— a qSOFA score of 2 or more is associated with a high risk of death or a prolonged stay in the intensive care unit.

Appendix G2. Criteria for systemic inflammatory response syndrome (SIRS)

Russian title: Systemic Inflammatory Response Syndrome Criteria

Original title: SIRS Criteria (Systemic Inflammatory Response Syndrome Criteria)

Source: Fernando SM, Tran A, Taljaard M, et al. Prognostic Accuracy of the Quick Sequential Organ Failure Assessment for Mortality in Patients With Suspected Infection: A Systematic Review and Meta-analysis. Annals of Internal Medicine 2018 February 20, 168 (4): 266-275

Type: rating scale

Purpose: screening to identify patients with sepsis

Content:

1. Body temperature >38°C or <36°C (Yes = 1; No = 0)

2. Heart rate >90/min (Yes = 1; No = 0)

3. Respiratory rate >20 breaths per minute or PaCO2 less than 32 mm Hg (4.3 kPa) (Yes = 1; No = 0)

4. Leukocyte count >12,000 /µL (>12 x10⁹/L) or <4,000 /µL (<4 x10⁹/L) (Yes = 1; No = 0)

Key (interpretation):

— 0 or 1 point: "Patient does not meet SIRS criteria"

— 2, 3, or 4 points: "Patient meets SIRS criteria. Please note that this does not diagnose infection"

Appendix G3. Modified Early Obstetric Warning System (MEOWS)

Russian title: Modified Early Obstetric Warning System

Original title: Modified Early Obstetric Warning System, MEOWS

Source (official developer website, validation publication): Singh A. et al. Evaluation of maternal early obstetric warning system (MEOWS chart) as a predictor of obstetric morbidity: a prospective observational study // Eur. J. Obstet. Gynecol. Reprod. Biol. Elsevier Ireland Ltd, 2016. Vol. 207. P. 11–17.

Type: rating scale

Purpose: early detection of sepsis and other critical conditions in obstetrics

Content:

Key (interpretation):

— Low risk – 1–4 points

— Moderate risk – 5–6 points

— High risk – 7 points or more.

Any single value of 3 points indicates an extreme deviation from the norm, which should be classified as at least the moderate-risk group.

Appendix G4. Sequential Organ Failure Assessment (SOFA) Score

Russian title: Sequential Organ Failure Assessment Scale SOFA

Original title: Sequential Organ Failure Assessment Score

Source: Singer M, Deutschman CS, Seymour CW, et al: The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 315:801–810, 2016. doi:10.1001/jama.2016.0287; Lambden S. et al. The SOFA score—development, utility and challenges of accurate assessment in clinical trials //Critical Care. – 2019. – Т. 23. – №. 1. – С. 1-9.

Type: rating scale

Purpose: evaluation of organ dysfunction

Content:

Key (interpretation):

The SOFA index is the sum of all six indicators

- minimum total score: 0

- maximum total score: 24

- the higher the score, the greater the organ dysfunction

- the higher the total score, the more severe the multiple organ dysfunction.