REVIEW URRENT C OPINION
Sepsis in obstetrics: cause, prevention, and treatment Jonathan M. Ford and Helen Scholefield
Purpose of review The aim of the study was to provide a summary of recent guidance on sepsis in obstetrics. Recent findings Morbidity and mortality from sepsis is increasing in the UK and other developed countries. In many cases, care has been found to be substandard. Common themes are a failure to recognize and respond to the sick woman and inadequate antibiotic and fluid management in the septic parturient. Summary Increased awareness of obstetric sepsis is required. Women and their families need to be informed about it and staff must have the skills and competencies to recognize this early. The management of severe sepsis in obstetrics is multidisciplinary. Implementation of the goals of the Surviving Sepsis Campaign into obstetric practice is important to improve outcomes. More research is needed to validate the parameters used in this and early warning scores for the obstetric population. Keywords antibiotic, obstetric sepsis, Surviving Sepsis Campaign
INTRODUCTION In September 2010, the United Kingdom Centre for Maternal and Child Enquiries published an ‘emergent theme briefing’ in advance of the full report to highlight sepsis as the new leading cause of direct maternal death. The full report covering the triennium 2006–2008 was published in March 2011 and reported that although most causes of direct maternal mortality had declined [1 ], direct maternal deaths from sepsis (genital tract sepsis) had risen from 0.85/100 000 [1 ] in the previous triennium to 1.13/100 000 maternities. There were 29 deaths in total from sepsis and the most common pathogen was Lancefield Group A Beta-hemolytic Streptococcus (Streptococcus pyogenes) accounting for 13 deaths [1 ]. The confidential enquiry highlighted that in a significant number of deaths, some aspect of medical care had been substandard and that with improved care, the outcome may have been different. The substandard care was focussed in three areas: &&
The confidential enquiry commented that ‘in the past, puerperal sepsis was a leading cause of maternal death and its signs and symptoms were widely known. The fear and respect with which it was held in the past by obstetricians, midwives, and patients has disappeared from our collective memory’. Action is now required to raise awareness of the signs and symptoms of sepsis and its recognition as a critical illness; this article aims to do this.
&&
&&
(1) Failure to recognize and respond to the sick woman. (2) Failures with antibiotic therapy. (3) Failure to manage fluid balance appropriately in the septic parturient.
CAUSES: RISK FACTORS All pregnant and recently delivered women are at risk of genital tract sepsis. Some women are at greater risk due to either the individual or obstetric risk factors. Individuals with impaired glucose tolerance, impaired immunity, anemia, or obesity (BMI >30) all have increased additional risk [2]. Women with sickle cell disease or sickle cell trait Department of Obstetrics, Liverpool Women’s NHS Foundation Trust, Liverpool, UK Correspondence to Dr Helen Scholefield, Consultant Obstetrician, Liverpool Women’s NHS Foundation Trust, Crown Street, Liverpool L8 7SS, UK. E-mail: [email protected] Curr Opin Anesthesiol 2014, 27:253–258 DOI:10.1097/ACO.0000000000000082
0952-7907 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
www.co-anesthesiology.com
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Obstetric and gynecological anesthesia
KEY POINTS Sepsis in obstetrics remains a major cause of maternal morbidity and mortality with Group A Streptococcus being the most commonly identified pathogen. Early warning scores help identify sick obstetric patients and should be used with an appropriate escalation care pathway. The sepsis bundle consisting of blood cultures and administration of broad-spectrum intravenous antibiotics within 1 h of suspecting sepsis should be followed. Relevant imaging techniques should be performed as appropriate and not withheld just because a woman is pregnant.
are at particular risk because of poor splenic function; they struggle to eliminate capsulated bacteria from their blood [1 ]. Women who require cervical cerclage, amniocentesis, or other invasive procedures also have increased risk for sepsis. Women with a history of Group B streptococcal infection or those identified as carriers antenatally using a vaginal or rectal swab are at greater risk [2]. Women who have prelabor rupture of membranes are at a higher risk of developing chorioamnionitis, especially if delivery does not occur within 48 h. These women require close monitoring and this is discussed later [2]. Twenty-one deaths were in pregnancies that continued beyond 24 weeks gestation, of which nine were delivered by cesarean section. This amounts to roughly double the rate occurring after vaginal birth. Onset of sepsis commenced after delivery in 20 of the 29 deaths. &&
PREVENTION OF DEATH FROM SEVERE SEPSIS Infection control measures are the main stay of prevention. The most important being hand washing and aseptic technique for invasive procedures. The Department of Health in the UK has published a number of ‘Saving Lives High Impact Interventions’, those for central and peripheral venous cannulation and urinary catheterization being especially important in this context [3]. An interesting observation in the confidential enquiry was that all of the women who died from group A streptococcal sepsis either worked with or had young children who commonly suffer from infections caused by this organism. Several mothers had a history of recent sore throat or respiratory infection. It is advised that women be made aware of the symptoms and need to seek advice early. They should also be told to wash their hands before and 254
www.co-anesthesiology.com
after using the toilet or change sanitary towels to avoid self-contamination, particularly if she or close contacts have a sore throat or upper respiratory tract infection. Antibiotic prophylaxis is important in the following situations: (1) periabortion [4]; (2) cesarean section [5]; (3) preterm/prolonged rupture of membranes [3]; and (4) third or fourth degree perineal tear [6]. There are national guidelines in the UK for all of these clinical situations.
EARLY RECOGNITION BY PROFESSIONALS: SYMPTOMS AND SIGNS Young healthy women can often maintain normal pulse and blood pressure in spite of insults such as postpartum hemorrhage and sepsis before suddenly becoming shocked and extremely unwell [2]. It is, therefore, important to have a low threshold for considering the diagnosis. The physiological changes of pregnancy such as increased heart rate, increased ventilation, and a fall in mean arterial pressure may further mask some of the initial clinical signs. Symptoms of sepsis may include diarrhea, vomiting, vaginal discharge, headache, urinary symptoms, or productive cough. Abdominal or pelvic pain, particularly if disproportionate to that which would be expected, may indicate infection. Persistent constant ache between contractions may be a symptom of infection such as chorioamnionitis (or abruption). Some women may simply present as feeling generally unwell with arthralgia and myalgia [7 ]. Breast pain is a sign of mastitis [8 ]. Clinical signs include pyrexia, hypothermia, tachycardia, hypotension, oliguria, and impaired consciousness [2]. Preterm labor may be caused by severe infection, especially in the presence of preterm rupture of membranes [2]. It is useful to ask specifically about a sore throat in the women or among her family members. Streptococcal sore throat is very common, especially among children and is easily spread via droplets. Contamination of the perineum with Group A Streptococcus is more likely to occur if the mother has a personal or family history suggestive of streptococcal sore throat [1 ]. &
&
&&
EARLY WARNING SCORES AND ESCALATION PATHWAYS &&
The latest triennial confidential enquiry report [1 ] again recommended the use of early warning scores Volume 27 Number 3 June 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Sepsis in obstetrics Ford and Scholefield
to help in more timely recognition, treatment, and referral of women who have or are developing a critical illness. Maternal early warning scores have been used for the past 9 years at Liverpool Women’s Hospital and found to be particularly effective in detecting sepsis. Early warning scores highlight the significance of a rising respiratory rate, an early marker of severe illness. Early warning scores need to be used with an escalation of care pathway. Figure 1 shows the one in use at the Liverpool Women’s Hospital.
INVESTIGATIONS Once sepsis is suspected in a pregnant or recently delivered woman, it is essential to culture all possible sources of infection. Blood, sputum, and urine should be sent for culture before antibiotics are administered [9 ]. Vaginal discharge, amniotic fluid, and breast milk may be collected and cultured. Throat, perineal, and abdominal wound swabs should also be sent. &&
A full blood count to identify leukocytosis (white blood cell count >12) or leukopenia (white blood cell count 160 bpm) may indicate infection of the liquor and membranes (chorioamnionitis), making delivery of the baby (or fetus) necessary on both fetal and maternal grounds. Ultrasound is the primary imaging technique of the pregnant abdomen and following delivery, a pelvic ultrasound will help exclude retained products of conception. It is important to bear in mind that sepsis can arise from nonobstetric causes. Conditions such as pneumonia, endocarditis, and peritonitis can all occur in the obstetric population. Chest radiographs [11], computed tomography scans [12], and echocardiography should be requested when indicated. Imaging should not be withheld just because a woman is pregnant. Fears of radiation exposure to her developing baby or sensitive maternal breast tissue need to be balanced against the clinical need for imaging.
TREATMENT The Surviving Sepsis Campaign Resuscitation Bundle applies well to the obstetric population. Following blood cultures, intravenous broad-spectrum antibiotics should be administered within 1 h of recognition of sepsis [9 ]. It is extremely important that this ‘golden hour’ for antibiotics is achieved as mortality increases almost exponentially with each hour of delay [13]. Figure 2 demonstrates the management tasks to be performed within 6 h following the identification of severe sepsis according to the Surviving Sepsis Campaign. In addition to clinical parameters, serum lactate is helpful in guiding fluid resuscitation and as a prognostic indicator for the need for admission to critical care. A particularly challenging part of managing the sepsis is fluid balance. Arterial hypotension in septic shock may be refractory to fluid resuscitation, leading &&
to fluid overload and pulmonary or cerebral edema. There are additional challenges in the parturient due to the physiology of pregnancy and commonly used drugs such as oxytocin and prostaglandins. Broad-spectrum antibiotics active against Gram-negative bacteria and capable of preventing exotoxin production from Gram-positive bacteria should be used [2]. The most commonly identified organisms are Lancefield group A beta-hemolytic Streptococcus and Escherichia coli. Local antimicrobial guidance should be followed and the early advice of microbiologist is essential. Commonly, a cephalosporin with metronidazole ensuring adequate coverage of anaerobic organisms is used until a specific pathogen is identified [1 ]. For moderate sepsis, tazocin and gentamicin would be better choices and for severe sepsis, merepenem and gentamicin. When considering dosage, it is important to understand the pathophysiology of severe sepsis in pregnancy, the infection site, and the pathogen. Hydrophilic drugs diffuse more slowly into deepseated infection, so a loading dose is more important. The target plasma concentration is affected by the increased volume of distribution in pregnancy and third spacing. There is also increased renal elimination due to the immune response, fluid loading, and use of vasoactive medications, which increase cardiac output and renal blood flow, prompting enhanced glomerular filtration and drug elimination [14]. Advice from a consultant microbiologist should be sought from an early stage [8 ]. Expert advice is particularly important when the patient fails to show signs of improvement following initial therapy or antibiotic resistance is suspected. Although high dependency unit care often exists on labor ward, obstetric patients may need higher level care. If required, pregnant patients should be transferred to intensive care. Most obstetric units would transfer women requiring inotrope support, mechanical ventilation, renal dialysis, or with multiorgan dysfunction [15]. Obstetricians and midwives are quite capable of visiting ICUs and pregnant &&
&
Surviving sepsis campaign resuscitation bundles – management tasks to be performed with 6 hours of identification of severe sepsis • Blood cultures prior to antibiotic administration • Administer broad-spectrum intravenous antibiotics within 1 hour of recognition of severe sepsis • Measure serum lactate (>4mmol/l reflects tissue hypoperfusion) • Intravenous fluid resuscitation
FIGURE 2. Demonstration of the clinical tasks to be completed within 6 h of diagnosing severe sepsis. This has been modified from [9 ]. &&
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Volume 27 Number 3 June 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Sepsis in obstetrics Ford and Scholefield
women should be cared for on them when clinically indicated. Once the woman starts to improve, the decision may be made for her care to be ‘stepped down’. This will usually be to an obstetric ward. Her antibiotics may be changed to the oral route. It is important that her antibiotic course is completed. The duration will normally be 7–10 days of antibiotics in total [1 ]. The woman must be reassured that her antibiotics are safe in pregnancy or breast-feeding as appropriate. Pediatricians should be informed of the mother’s condition. If delivery is imminent, her baby may be born in poor condition or septic. Even if the mother is postnatal, it is useful to inform the neonatal unit of her condition, as this may prompt greater surveillance of her baby, provision of antibiotics, or alter the choice of antibiotics for her baby [2]. This is especially the case if a particular pathogen is cultured. &&
SPECIFIC PROBLEMS IN OBSTETRICS Approximately, 2% of pregnancies are complicated by preterm prelabor rupture of membranes [2]. Women often present with a history of a ‘sudden loss of fluid’ and this is usually confirmed when liquor is seen pooling in the posterior fornix on speculum examination at gestations less than 37 weeks. At gestations below 34 weeks, guidance suggests conservative management [2]. These women require close surveillance and are either managed as inpatients or on obstetric day units with a least twice weekly review. Regular review of symptoms, maternal observations, and blood results can identify developing chorioamnionitis before the mother or her baby develops sepsis allowing earlier delivery. In previable pregnancies such as those less than 24 weeks gestation or with estimated fetal weight below 500 g when the mother is becoming unwell, it is also necessary to deliver the baby. In these situations, we are ending or terminating the pregnancy to ensure the mother does not become septic. Delivery is induced by administering either syntocinon or misoprostol. Both these agents provoke uterine contractions and subsequent vaginal delivery of the fetus. In the presence of chorioamnionitis, if the baby or fetus is not delivered, the focus of infection remains and despite appropriate intravenous antibiotics, the mother may die. Persistent or swinging pyrexia or failure to respond to antibiotics may indicate the presence of an abscess or collection. These can be identified and imaged using computed tomography or
&
ultrasound scanning [8 ]. Postoperative collection or abscess formation in a septic patient requires drainage [1 ]. Intravenous antibiotics will not penetrate the collection. Antibiotics may treat the bactereamia however they will not treat the underlying pathology and the collection will remain. Either surgical or radiological drainage is indicated in these circumstances. General surgeons may need to be involved if the woman requires a surgical intervention [8 ]. &&
&
CONCLUSION Obstetric patients, like all patients, can become unwell and sepsis remains a major cause of this. Thinking of sepsis and efficiently applying the sepsis bundle can effectively treat these women. Twenty-six women dying of genital tract sepsis in 3 years may not seem a massive number however as the authors of the CMACE report 2006–2008 eloquently state ‘the death of a mother, a young woman who had hopes and dreams for a happy future but who dies before her time, is one of the cruelest events imaginable’, something we can help to prevent. Acknowledgements None. Conflicts of interest There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Centre for Maternal and Child Enquiries (CMACE). Saving Mothers’ Lives: reviewing maternal deaths to make motherhood safer: 2006–08. The Eighth Report on Confidential Enquiries into Maternal Deaths in the United Kingdom. BJOG 2011; 118 (Suppl 1):1–203. Triennial report reviewing all maternal deaths in the United Kingdom during 2006– 2008. It provides insight into the various causes of maternal mortality focusing on the care women received and how we can reduce maternal mortality in the future. Identified genital sepsis as the leading cause of direct maternal deaths with a maternal mortality rate of 1.13/100 000 maternities. 2. Royal College of Obstetricians and Gynaecologists. Greentop Guideline No 44: Preterm Prelabour Rupture of Membranes. London. RCOG; 2010. 3. Department of Health. Saving Lives: reducing infection, delivering clean and safe care. June 2007. 4. Royal College of Obstetricians and Gynaecologists. Evidence Based Clinical Guideline No 7: the care of women requesting induced abortion. London. RCOG; 2011. 5. National Institute for Health and Clinical Excellence. NICE clinical guideline 132: caesaren section. London. NICE; 2011. 6. Royal College of Obstetricians and Gynaecologists. Greentop Guideline No.29. Third and Fourth Degree Perineal Tears. London. RCOG; 2007. 7. Royal College of Obstetricians and Gynaecologists. Greentop Guideline No. & 64a: Bacterial Sepsis in Pregnancy. London. RCOG; 2012. Evidence-based guideline produced by the ROCG identifying high-risk patient groups, diagnosis, and management of bacterial sepsis in pregnancy. Highlights common bacterial pathogens in pregnancy and details appropriate antibiotic therapy.
&&
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www.co-anesthesiology.com
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Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Obstetric and gynecological anesthesia 8. Royal College of Obstetricians and Gynaecologists. Greentop Guide& line No. 64b:Bacterial Sepsis following Pregnancy. London. RCOG; 2012. Evidence-based guideline produced by the RCOG detailing the various causes of bacterial sepsis following pregnancy. Indicates criteria for women requiring hospital admission and those requiring intensive care treatment. Discusses public health issues, including prophylaxis for family members. 9. Surviving Sepsis Campaign: International Guidelines for Management of && Severe Sepsis and Septic Shock; 2012 Evidence-based guideline reflecting international consensus for the management of severe sepsis. Defines sepsis and severe sepsis, including their diagnostic criteria. Details the role of the sepsis bundle and the management of patients who do not respond to initial management and require intensive care treatment.
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10. Wacker C, Prkno A, Brunkhorst FM, et al. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis 2013; 13:426–435. 11. Damilakis J, Perisinakis K, Prassoupoulos P, et al. Conceptus radiation dose and risk from chest screen-film radiography. Eur J Radiol 2003; 13:406–412. 12. Cook JV, Kyrious J. Radiation from CT and perfusion scanning in pregnancy. Br Med J 2005; 331–350. 13. Butt M, Coulson A, Hull J, Ho T. Bloodstream infection: early treatment strategies in sepsis. BMJ 2008; 336:521.1. 14. Fuster-Lluch O, Geronimo-Pardo M, Peyro-Garcia R, et al. Glomerular hyperfiltration and albuminuria in critically ill patients. Anaesth Intensive Care 2008; 36:674–680. 15. Plaat F, Wray S. Role of the anaesthetist in obstetric critical care. Best Pract Res Clin Obstet Gynaecol 2008; 22:917–935.
Volume 27 Number 3 June 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Sepsis in obstetrics: cause, prevention, and treatment Jonathan M. Ford and Helen Scholefield
Purpose of review The aim of the study was to provide a summary of recent guidance on sepsis in obstetrics. Recent findings Morbidity and mortality from sepsis is increasing in the UK and other developed countries. In many cases, care has been found to be substandard. Common themes are a failure to recognize and respond to the sick woman and inadequate antibiotic and fluid management in the septic parturient. Summary Increased awareness of obstetric sepsis is required. Women and their families need to be informed about it and staff must have the skills and competencies to recognize this early. The management of severe sepsis in obstetrics is multidisciplinary. Implementation of the goals of the Surviving Sepsis Campaign into obstetric practice is important to improve outcomes. More research is needed to validate the parameters used in this and early warning scores for the obstetric population. Keywords antibiotic, obstetric sepsis, Surviving Sepsis Campaign
INTRODUCTION In September 2010, the United Kingdom Centre for Maternal and Child Enquiries published an ‘emergent theme briefing’ in advance of the full report to highlight sepsis as the new leading cause of direct maternal death. The full report covering the triennium 2006–2008 was published in March 2011 and reported that although most causes of direct maternal mortality had declined [1 ], direct maternal deaths from sepsis (genital tract sepsis) had risen from 0.85/100 000 [1 ] in the previous triennium to 1.13/100 000 maternities. There were 29 deaths in total from sepsis and the most common pathogen was Lancefield Group A Beta-hemolytic Streptococcus (Streptococcus pyogenes) accounting for 13 deaths [1 ]. The confidential enquiry highlighted that in a significant number of deaths, some aspect of medical care had been substandard and that with improved care, the outcome may have been different. The substandard care was focussed in three areas: &&
The confidential enquiry commented that ‘in the past, puerperal sepsis was a leading cause of maternal death and its signs and symptoms were widely known. The fear and respect with which it was held in the past by obstetricians, midwives, and patients has disappeared from our collective memory’. Action is now required to raise awareness of the signs and symptoms of sepsis and its recognition as a critical illness; this article aims to do this.
&&
&&
(1) Failure to recognize and respond to the sick woman. (2) Failures with antibiotic therapy. (3) Failure to manage fluid balance appropriately in the septic parturient.
CAUSES: RISK FACTORS All pregnant and recently delivered women are at risk of genital tract sepsis. Some women are at greater risk due to either the individual or obstetric risk factors. Individuals with impaired glucose tolerance, impaired immunity, anemia, or obesity (BMI >30) all have increased additional risk [2]. Women with sickle cell disease or sickle cell trait Department of Obstetrics, Liverpool Women’s NHS Foundation Trust, Liverpool, UK Correspondence to Dr Helen Scholefield, Consultant Obstetrician, Liverpool Women’s NHS Foundation Trust, Crown Street, Liverpool L8 7SS, UK. E-mail: [email protected] Curr Opin Anesthesiol 2014, 27:253–258 DOI:10.1097/ACO.0000000000000082
0952-7907 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
www.co-anesthesiology.com
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Obstetric and gynecological anesthesia
KEY POINTS Sepsis in obstetrics remains a major cause of maternal morbidity and mortality with Group A Streptococcus being the most commonly identified pathogen. Early warning scores help identify sick obstetric patients and should be used with an appropriate escalation care pathway. The sepsis bundle consisting of blood cultures and administration of broad-spectrum intravenous antibiotics within 1 h of suspecting sepsis should be followed. Relevant imaging techniques should be performed as appropriate and not withheld just because a woman is pregnant.
are at particular risk because of poor splenic function; they struggle to eliminate capsulated bacteria from their blood [1 ]. Women who require cervical cerclage, amniocentesis, or other invasive procedures also have increased risk for sepsis. Women with a history of Group B streptococcal infection or those identified as carriers antenatally using a vaginal or rectal swab are at greater risk [2]. Women who have prelabor rupture of membranes are at a higher risk of developing chorioamnionitis, especially if delivery does not occur within 48 h. These women require close monitoring and this is discussed later [2]. Twenty-one deaths were in pregnancies that continued beyond 24 weeks gestation, of which nine were delivered by cesarean section. This amounts to roughly double the rate occurring after vaginal birth. Onset of sepsis commenced after delivery in 20 of the 29 deaths. &&
PREVENTION OF DEATH FROM SEVERE SEPSIS Infection control measures are the main stay of prevention. The most important being hand washing and aseptic technique for invasive procedures. The Department of Health in the UK has published a number of ‘Saving Lives High Impact Interventions’, those for central and peripheral venous cannulation and urinary catheterization being especially important in this context [3]. An interesting observation in the confidential enquiry was that all of the women who died from group A streptococcal sepsis either worked with or had young children who commonly suffer from infections caused by this organism. Several mothers had a history of recent sore throat or respiratory infection. It is advised that women be made aware of the symptoms and need to seek advice early. They should also be told to wash their hands before and 254
www.co-anesthesiology.com
after using the toilet or change sanitary towels to avoid self-contamination, particularly if she or close contacts have a sore throat or upper respiratory tract infection. Antibiotic prophylaxis is important in the following situations: (1) periabortion [4]; (2) cesarean section [5]; (3) preterm/prolonged rupture of membranes [3]; and (4) third or fourth degree perineal tear [6]. There are national guidelines in the UK for all of these clinical situations.
EARLY RECOGNITION BY PROFESSIONALS: SYMPTOMS AND SIGNS Young healthy women can often maintain normal pulse and blood pressure in spite of insults such as postpartum hemorrhage and sepsis before suddenly becoming shocked and extremely unwell [2]. It is, therefore, important to have a low threshold for considering the diagnosis. The physiological changes of pregnancy such as increased heart rate, increased ventilation, and a fall in mean arterial pressure may further mask some of the initial clinical signs. Symptoms of sepsis may include diarrhea, vomiting, vaginal discharge, headache, urinary symptoms, or productive cough. Abdominal or pelvic pain, particularly if disproportionate to that which would be expected, may indicate infection. Persistent constant ache between contractions may be a symptom of infection such as chorioamnionitis (or abruption). Some women may simply present as feeling generally unwell with arthralgia and myalgia [7 ]. Breast pain is a sign of mastitis [8 ]. Clinical signs include pyrexia, hypothermia, tachycardia, hypotension, oliguria, and impaired consciousness [2]. Preterm labor may be caused by severe infection, especially in the presence of preterm rupture of membranes [2]. It is useful to ask specifically about a sore throat in the women or among her family members. Streptococcal sore throat is very common, especially among children and is easily spread via droplets. Contamination of the perineum with Group A Streptococcus is more likely to occur if the mother has a personal or family history suggestive of streptococcal sore throat [1 ]. &
&
&&
EARLY WARNING SCORES AND ESCALATION PATHWAYS &&
The latest triennial confidential enquiry report [1 ] again recommended the use of early warning scores Volume 27 Number 3 June 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Sepsis in obstetrics Ford and Scholefield
to help in more timely recognition, treatment, and referral of women who have or are developing a critical illness. Maternal early warning scores have been used for the past 9 years at Liverpool Women’s Hospital and found to be particularly effective in detecting sepsis. Early warning scores highlight the significance of a rising respiratory rate, an early marker of severe illness. Early warning scores need to be used with an escalation of care pathway. Figure 1 shows the one in use at the Liverpool Women’s Hospital.
INVESTIGATIONS Once sepsis is suspected in a pregnant or recently delivered woman, it is essential to culture all possible sources of infection. Blood, sputum, and urine should be sent for culture before antibiotics are administered [9 ]. Vaginal discharge, amniotic fluid, and breast milk may be collected and cultured. Throat, perineal, and abdominal wound swabs should also be sent. &&
A full blood count to identify leukocytosis (white blood cell count >12) or leukopenia (white blood cell count 160 bpm) may indicate infection of the liquor and membranes (chorioamnionitis), making delivery of the baby (or fetus) necessary on both fetal and maternal grounds. Ultrasound is the primary imaging technique of the pregnant abdomen and following delivery, a pelvic ultrasound will help exclude retained products of conception. It is important to bear in mind that sepsis can arise from nonobstetric causes. Conditions such as pneumonia, endocarditis, and peritonitis can all occur in the obstetric population. Chest radiographs [11], computed tomography scans [12], and echocardiography should be requested when indicated. Imaging should not be withheld just because a woman is pregnant. Fears of radiation exposure to her developing baby or sensitive maternal breast tissue need to be balanced against the clinical need for imaging.
TREATMENT The Surviving Sepsis Campaign Resuscitation Bundle applies well to the obstetric population. Following blood cultures, intravenous broad-spectrum antibiotics should be administered within 1 h of recognition of sepsis [9 ]. It is extremely important that this ‘golden hour’ for antibiotics is achieved as mortality increases almost exponentially with each hour of delay [13]. Figure 2 demonstrates the management tasks to be performed within 6 h following the identification of severe sepsis according to the Surviving Sepsis Campaign. In addition to clinical parameters, serum lactate is helpful in guiding fluid resuscitation and as a prognostic indicator for the need for admission to critical care. A particularly challenging part of managing the sepsis is fluid balance. Arterial hypotension in septic shock may be refractory to fluid resuscitation, leading &&
to fluid overload and pulmonary or cerebral edema. There are additional challenges in the parturient due to the physiology of pregnancy and commonly used drugs such as oxytocin and prostaglandins. Broad-spectrum antibiotics active against Gram-negative bacteria and capable of preventing exotoxin production from Gram-positive bacteria should be used [2]. The most commonly identified organisms are Lancefield group A beta-hemolytic Streptococcus and Escherichia coli. Local antimicrobial guidance should be followed and the early advice of microbiologist is essential. Commonly, a cephalosporin with metronidazole ensuring adequate coverage of anaerobic organisms is used until a specific pathogen is identified [1 ]. For moderate sepsis, tazocin and gentamicin would be better choices and for severe sepsis, merepenem and gentamicin. When considering dosage, it is important to understand the pathophysiology of severe sepsis in pregnancy, the infection site, and the pathogen. Hydrophilic drugs diffuse more slowly into deepseated infection, so a loading dose is more important. The target plasma concentration is affected by the increased volume of distribution in pregnancy and third spacing. There is also increased renal elimination due to the immune response, fluid loading, and use of vasoactive medications, which increase cardiac output and renal blood flow, prompting enhanced glomerular filtration and drug elimination [14]. Advice from a consultant microbiologist should be sought from an early stage [8 ]. Expert advice is particularly important when the patient fails to show signs of improvement following initial therapy or antibiotic resistance is suspected. Although high dependency unit care often exists on labor ward, obstetric patients may need higher level care. If required, pregnant patients should be transferred to intensive care. Most obstetric units would transfer women requiring inotrope support, mechanical ventilation, renal dialysis, or with multiorgan dysfunction [15]. Obstetricians and midwives are quite capable of visiting ICUs and pregnant &&
&
Surviving sepsis campaign resuscitation bundles – management tasks to be performed with 6 hours of identification of severe sepsis • Blood cultures prior to antibiotic administration • Administer broad-spectrum intravenous antibiotics within 1 hour of recognition of severe sepsis • Measure serum lactate (>4mmol/l reflects tissue hypoperfusion) • Intravenous fluid resuscitation
FIGURE 2. Demonstration of the clinical tasks to be completed within 6 h of diagnosing severe sepsis. This has been modified from [9 ]. &&
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Volume 27 Number 3 June 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Sepsis in obstetrics Ford and Scholefield
women should be cared for on them when clinically indicated. Once the woman starts to improve, the decision may be made for her care to be ‘stepped down’. This will usually be to an obstetric ward. Her antibiotics may be changed to the oral route. It is important that her antibiotic course is completed. The duration will normally be 7–10 days of antibiotics in total [1 ]. The woman must be reassured that her antibiotics are safe in pregnancy or breast-feeding as appropriate. Pediatricians should be informed of the mother’s condition. If delivery is imminent, her baby may be born in poor condition or septic. Even if the mother is postnatal, it is useful to inform the neonatal unit of her condition, as this may prompt greater surveillance of her baby, provision of antibiotics, or alter the choice of antibiotics for her baby [2]. This is especially the case if a particular pathogen is cultured. &&
SPECIFIC PROBLEMS IN OBSTETRICS Approximately, 2% of pregnancies are complicated by preterm prelabor rupture of membranes [2]. Women often present with a history of a ‘sudden loss of fluid’ and this is usually confirmed when liquor is seen pooling in the posterior fornix on speculum examination at gestations less than 37 weeks. At gestations below 34 weeks, guidance suggests conservative management [2]. These women require close surveillance and are either managed as inpatients or on obstetric day units with a least twice weekly review. Regular review of symptoms, maternal observations, and blood results can identify developing chorioamnionitis before the mother or her baby develops sepsis allowing earlier delivery. In previable pregnancies such as those less than 24 weeks gestation or with estimated fetal weight below 500 g when the mother is becoming unwell, it is also necessary to deliver the baby. In these situations, we are ending or terminating the pregnancy to ensure the mother does not become septic. Delivery is induced by administering either syntocinon or misoprostol. Both these agents provoke uterine contractions and subsequent vaginal delivery of the fetus. In the presence of chorioamnionitis, if the baby or fetus is not delivered, the focus of infection remains and despite appropriate intravenous antibiotics, the mother may die. Persistent or swinging pyrexia or failure to respond to antibiotics may indicate the presence of an abscess or collection. These can be identified and imaged using computed tomography or
&
ultrasound scanning [8 ]. Postoperative collection or abscess formation in a septic patient requires drainage [1 ]. Intravenous antibiotics will not penetrate the collection. Antibiotics may treat the bactereamia however they will not treat the underlying pathology and the collection will remain. Either surgical or radiological drainage is indicated in these circumstances. General surgeons may need to be involved if the woman requires a surgical intervention [8 ]. &&
&
CONCLUSION Obstetric patients, like all patients, can become unwell and sepsis remains a major cause of this. Thinking of sepsis and efficiently applying the sepsis bundle can effectively treat these women. Twenty-six women dying of genital tract sepsis in 3 years may not seem a massive number however as the authors of the CMACE report 2006–2008 eloquently state ‘the death of a mother, a young woman who had hopes and dreams for a happy future but who dies before her time, is one of the cruelest events imaginable’, something we can help to prevent. Acknowledgements None. Conflicts of interest There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Centre for Maternal and Child Enquiries (CMACE). Saving Mothers’ Lives: reviewing maternal deaths to make motherhood safer: 2006–08. The Eighth Report on Confidential Enquiries into Maternal Deaths in the United Kingdom. BJOG 2011; 118 (Suppl 1):1–203. Triennial report reviewing all maternal deaths in the United Kingdom during 2006– 2008. It provides insight into the various causes of maternal mortality focusing on the care women received and how we can reduce maternal mortality in the future. Identified genital sepsis as the leading cause of direct maternal deaths with a maternal mortality rate of 1.13/100 000 maternities. 2. Royal College of Obstetricians and Gynaecologists. Greentop Guideline No 44: Preterm Prelabour Rupture of Membranes. London. RCOG; 2010. 3. Department of Health. Saving Lives: reducing infection, delivering clean and safe care. June 2007. 4. Royal College of Obstetricians and Gynaecologists. Evidence Based Clinical Guideline No 7: the care of women requesting induced abortion. London. RCOG; 2011. 5. National Institute for Health and Clinical Excellence. NICE clinical guideline 132: caesaren section. London. NICE; 2011. 6. Royal College of Obstetricians and Gynaecologists. Greentop Guideline No.29. Third and Fourth Degree Perineal Tears. London. RCOG; 2007. 7. Royal College of Obstetricians and Gynaecologists. Greentop Guideline No. & 64a: Bacterial Sepsis in Pregnancy. London. RCOG; 2012. Evidence-based guideline produced by the ROCG identifying high-risk patient groups, diagnosis, and management of bacterial sepsis in pregnancy. Highlights common bacterial pathogens in pregnancy and details appropriate antibiotic therapy.
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Obstetric and gynecological anesthesia 8. Royal College of Obstetricians and Gynaecologists. Greentop Guide& line No. 64b:Bacterial Sepsis following Pregnancy. London. RCOG; 2012. Evidence-based guideline produced by the RCOG detailing the various causes of bacterial sepsis following pregnancy. Indicates criteria for women requiring hospital admission and those requiring intensive care treatment. Discusses public health issues, including prophylaxis for family members. 9. Surviving Sepsis Campaign: International Guidelines for Management of && Severe Sepsis and Septic Shock; 2012 Evidence-based guideline reflecting international consensus for the management of severe sepsis. Defines sepsis and severe sepsis, including their diagnostic criteria. Details the role of the sepsis bundle and the management of patients who do not respond to initial management and require intensive care treatment.
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10. Wacker C, Prkno A, Brunkhorst FM, et al. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis 2013; 13:426–435. 11. Damilakis J, Perisinakis K, Prassoupoulos P, et al. Conceptus radiation dose and risk from chest screen-film radiography. Eur J Radiol 2003; 13:406–412. 12. Cook JV, Kyrious J. Radiation from CT and perfusion scanning in pregnancy. Br Med J 2005; 331–350. 13. Butt M, Coulson A, Hull J, Ho T. Bloodstream infection: early treatment strategies in sepsis. BMJ 2008; 336:521.1. 14. Fuster-Lluch O, Geronimo-Pardo M, Peyro-Garcia R, et al. Glomerular hyperfiltration and albuminuria in critically ill patients. Anaesth Intensive Care 2008; 36:674–680. 15. Plaat F, Wray S. Role of the anaesthetist in obstetric critical care. Best Pract Res Clin Obstet Gynaecol 2008; 22:917–935.
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