Monday, September 27, 2021

Septic Shock Case File

Posted By: Medical Group - 9/27/2021 Post Author : Medical Group Post Date : Monday, September 27, 2021 Post Time : 9/27/2021
Septic Shock Case File
Eugene C. Toy, MD, Edward Yeomans, MD, Linda Fonseca, MD, Joseph M. Ernest, MD

Case 34
An 18-year-old G1P0 woman at 22 weeks’ gestation was admitted to the hospital with a 2-day history of fever, chills, and flank pain. Examination revealed a temperature of 103°F and marked costovertebral
angle tenderness on the right. Urinalysis showed 4+ bacteria and many WBCs. Urine and blood cultures were obtained intravenous and ceftriaxone was begun for presumptive pyelonephritis. Lactated Ringer solution was ordered intravenously at 125 cc/h. The next morning, the patient was found to have a blood pressure of 70/30 mm Hg, a temperature of 96°F, pulse of 140 bpm, and respirations of 36 breaths per minute. Her urine output over the previous 12 hours was 200 cc.

➤ What complication of pyelonephritis has she developed?
➤ What is the pathophysiology of this condition?
➤ How should this condition be managed?


ANSWER TO CASE 34:
Septic Shock

Summary: An 18-year-old G1P0 at 22 weeks was admitted to the hospital, diagnosed with pyelonephritis and begun on a suitable intravenous antibiotic. In less than 24 hours, she developed septic shock.

Complication of pyelonephritis developed: Septic shock. Shortly after initiating IV antibiotic therapy for pyelonephritis is a time of increased risk for the development of septic shock.

Pathophysiology of this condition: Most cases of pyelonephritis in pregnancy are due to infection by gram-negative aerobic bacteria, Escherichia coli being the most frequent causative agent. Antibiotic therapy causes lysis of bacteria, and this in turn leads to release of endotoxin. Endotoxin triggers a host inflammatory response culminating in hypotension, decreased tissue perfusion, and septic shock.

Management of this condition: The short answer to this question is that septic shock must be managed aggressively. The plan of management consists of early goal-directed therapy characterized by fluid resuscitation, broad spectrum antibiotics, and, if needed, vasopressors to maintain mean arterial pressure above 65 mm Hg. Details are provided in the section Clinical Approach.


ANALYSIS
Objectives
  1. Identify the most common obstetric antecedents of septic shock.
  2. Review the characteristics of the bacteria that are most commonly etiologic in septic shock in pregnancy.
  3. Outline the evolving management of septic shock in pregnancy and the immediate postpartum period.

Considerations
The woman in the case scenario presented with classic signs and symptoms of pyelonephritis. Most cases of pyelonephritis in pregnancy are caused by infection with gram-negative aerobic bacteria, but an increasing number are due to group B Streptococcus. In this series of 440 pregnant women hospitalized with acute pyelonephritis, more than half of whom were in their second trimester (as in our case), there were no cases of septic shock specifically mentioned.However, 7% of the women developed pulmonary insufficiency, presumably related to release of endotoxin. In contrast, when the question is reversed, that is, not how many cases of septic shock occurred in pregnant women diagnosed with pyelonephritis, but instead how many cases of pyelonephritis were found in a series of pregnant women with septic shock, pyelonephritis was the leading cause of septic shock in one report2, accounting for 6 of 18 cases. It is not definitely known whether early diagnosis and aggressive treatment of pyelonephritis in pregnancy would interdict its progression to septic shock, but it makes sense that it would.

APPROACH TO
Septic Shock

DEFINITIONS

ENDOTOXIN: A bacterial toxin not freely released into the surrounding tissue or fluid. It is a lipopolysaccharide component of the cell wall of especially gram-negative aerobic bacteria. Its release occurs only upon injury or damage to the bacterial cell wall, which, as in the case described, occasionally occurs after the initiation of treatment.

EXOTOXIN: Also a bacterial toxin, but produced by gram-positive bacteria and readily liberated into tissue or fluid. Exotoxins are very potent and rapidly active even when secreted in very small amounts. In the recent obstetric literature exotoxins have accounted for an increasing percentage of cases of sepsis syndrome, septic shock representing the most extreme manifestation of the sepsis syndrome.

SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (SIRS): A response of the host, in our setting generated by infection (but in other settings capable of being caused by noninfectious entities like trauma or burns). It is manifested by two or more of the following criteria: hyperthermia (> 38°C) or hypothermia (< 36°C), tachycardia (HR > 90 bpm), tachypnea (> 20 breaths per minute) or hypocarbia (PaCO2 < 32 mm Hg), abnormal white blood cell count (> 12,000 or < 4000), bandemia (> 10% bands). Importantly, SIRS criteria have not been developed specifically for pregnancy. Also, the definition of SIRS excludes hypotension. Once hypotension develops and persists despite adequate fluid resuscitation, the condition has progressed to septic shock.


CLINICAL APPROACH
This section of the chapter is organized around the three objectives previously stated. According to one expert, septic shock, which accounts for 215,000 deaths per year in the United States, is one of the most challenging problems in all of critical care medicine.3 Fortunately for obstetricians, it is relatively rare in pregnancy, occurring with a frequency of 1 per 8000 deliveries.Accordingly, there are relatively few reports on septic shock complicating either pregnancy or the puerperium and no trials of therapy conducted exclusively in pregnant women. The most common obstetric antecedents of septic shock are: pyelonephritis, septic abortion, chorioamnionitis, endometritis, and necrotizing fasciitis. Prior to the Supreme Court ruling on Roe v. Wade, septic abortion was the most common of these and it still predominates in countries where abortion is illegal. At the present time in the United States, pyelonephritis is the leading cause of septic shock in pregnant women.

Although many different bacteria are capable of inciting septic shock, only relatively few are important causes of obstetric infection. The predominant gram-negative causes of septic shock can be remembered by the acronym EEKPP—Escherichia, Enterobacter, Klebsiella, Proteus, and Pseudomonas. Endotoxin released by these agents incites an intense inflammatory response in the host, which then leads to vasodilation, hypotension, inadequate tissue perfusion, lactic acidosis, and, if not reversed, death. Monomicrobial infection is most often seen with pyelonephritis, whereas most other obstetric infections are polymicrobial, and therefore require broad-spectrum antimicrobial therapy, often with multiple agents.

More recently, there has been an upsurge of infections caused by grampositive organisms including Staphylococci (especially methicillin-resistant subtypes that are either hospital-acquired or community-acquired), group A Streptococci, and Clostridium sordellii. These bacteria elaborate powerful exotoxins that can cause widespread tissue destruction.5-7 The obstetric literature pertaining to these gram-positive infections consists mainly of case reports or very small series. Andrews et al5 described a woman who developed toxic shock due to methicillin-resistant Staphylococcus aureus (MRSA) 4 weeks after a cesarean delivery. The staphylococcus was not identified until hospital day 9, when culture of a left-breast aspirate identified the organism. A toxin assay after discharge from the hospital confirmed the presence of enterotoxin B, one of the three toxins (the other two are enterotoxin C and toxic shock syndrome toxin 1) known to be associated with staphylococcal toxic shock; half of all cases are nonmenstrual.

Obstetric cases have been reported after vaginal and cesarean deliveries, postpartum wound infections, and mastitis. A heart-wrenching case of necrotizing fasciitis after cesarean delivery was reported by deMoya and colleagues.In this case the infecting organism was group A Streptococcus, reported to be more lethal than Staphylococcus. Group A Streptococcus elaborates several exotoxins, for example, exotoxin A, along with other proteins that act as superantigens, triggering massive release of cytokines. The unfortunate patient survived, but with loss of her entire abdominal wall, uterus, tubes, ovaries, gallbladder, right colon, and all four extremities. Lastly, Cohen and colleaguesreported four cases of toxic shock following either medical or spontaneous abortion associated with infection by Clostridium species, two with perfringens and two with sordellii. Clostridium sordellii secretes a potent exotoxin identified as cytotoxin L (L for lethal). All four patients had a rapidly progressive illness with necrotizing endomyometritis and three of the four died.

It is apparent, then, that bacteria and/or their component toxins can produce a sepsis syndrome that, unchecked, will develop into septic shock. The cornerstone of management is early diagnosis, but often that is not easy. A program of early goal-directed therapy8 has been shown to reduce mortality from septic shock. However, not all patients with septic shock require the same treatment interventions. The woman in our case scenario, for example, requires aggressive fluid resuscitation and transfer to an intensive care unit. Per hour 1 to 2 L (not the 125 cc/h she was receiving) would be appropriate.
The total volume needed should be determined by monitoring central venous pressure. An arterial catheter should be placed to monitor blood pressure and obtain timely pH and blood gas measurements. If adequate fluid resuscitation has not elevated the mean arterial pressure above 65 mm Hg, then vasopressors would be indicated. Adequate oxygenation should be maintained, with endotracheal intubation and mechanical ventilation, if necessary. The ceftriaxone she was receiving likely does not need to be changed, but some authorities1 prefer ampicillin and gentamicin for the treatment of pyelonephritis in pregnancy. Surgical intervention is seldom necessary for septic shock secondary to pyelonephritis, but prolonged hypotension and ischemia can lead to gangrene of the extremities and amputation in severe cases. When septic shock results from necrotizing fasciitis, extensive debridement of necrotic tissue is an essential component of management. Antibiotic therapy should include vancomycin for methicillin-resistant Staphylococcus and clindamycin for Streptococcus; there is evidence that clindamycin may directly inhibit synthesis of group A streptococcal toxins.

The sequelae of septic shock depend on the duration and severity of the insult. Conditions that are associated with septic shock like acute renal failure, acute respiratory distress syndrome (ARDS), DIC, and abnormal liver function are best managed in an intensive care unit. From the literature, the more organ systems that are involved, the worse the prognosis.

The high mortality associated with septic shock has engendered an impressive number of randomized clinical trials of adjunctive therapies of agents including high-and low-dose corticosteroids, ibuprofen, vasopressin, insulin, activated protein C, and others. The results of such trials are conflicting, inconclusive, or negative in most instances.

Finally, three of the five obstetric antecedents (chorioamnionitis, endometritis, and septic abortion) of septic shock involve infection of the uterus. Necrosis of the uterus, tubes, and ovaries can also complicate necrotizing fasciitis.6 Therefore, laparotomy with hysterectomy and possible adnexectomy are crucial interventions that an obstetrician-gynecologist may need to undertake to save the life of his or her patient.


Comprehension Questions

34.1 In obstetrics which of the following diagnoses is the leading cause of septic shock?
A. Necrotizing fasciitis
B. Pyelonephritis
C. Chorioamnionitis
D. Endometritis

34.2 Which of the following bacteria elaborates cytotoxin L?
A. Group A Streptococcus
B. Escherichia Coli
C. MRSA
D. Clostridium sordellii

34.3 Which of the following criteria for systemic inflammatory response syndrome (SIRS) is most likely to be affected by altered physiology in pregnancy?
A. Temperature of 39°C
B. Pulse > 90 bpm
C. PCO2 < 32 mmHg
D. WBC > 12,000/mm3


ANSWERS

34.1 B. As mentioned in the chapter, there are very few series of septic shock in pregnancy. The answer to this question can be found on page 676 of reference 4.

34.2 D. Cytotoxin L has been found in cases of Clostridium sordellii infection related to abortion (for extended discussion, see reference 7).

34.3 C. Progesterone increases during pregnancy stimulates the respiratory center and minute volume increases. PCO2 is inversely related to minute volume and is therefore reset to a mean of 30 mm Hg. This is the best answer, but choice B has merit as well, since heart rate increases physiologically during pregnancy.


Clinical Pearls

See US Preventive Services Task Force Study Quality levels of evidence in Case 1
➤ Pyelonephritis is one of the most common serious medical complications of pregnancy. Only a few cases result in serious sequelae like ARDS or septic shock—stay alert! (Level III)
➤ Systemic vascular resistance normally decreases in pregnancy, but nowhere near the level seen in septic shock (≤ 400 dyne/sec/cm−5). Such profound vasodilation necessitates aggressive fluid resuscitation and possibly exogenous vasopressors (Level II-3).
➤ Necrotizing fasciitis complicates 1 to 2 per 1000 cesarean deliveries and the cesarean rate is steadily rising. Risk factors include diabetes, obesity, and hypertension—all commonly encountered in pregnant women. Early diagnosis and extensive debridement may prevent septic shock (Level III).

REFERENCES

1. Hill JB, Sheffield JS, McIntire DD, Wendel GD Jr. Acute pyelonephritis in pregnancy. Obstet Gynecol. 2005;105:18-23. 

2. Mabie WC, Barton JR, Sibai B. Septic shock in pregnancy. Obstet Gynecol. 1997;90:553-561. 

3. Parillo JE. Septic shock—vasopressin, norepinephrine, and urgency. N Engl J Med. 2008;358:954-956. 

4. Martin SR, Foley MR. Intensive care in obstetrics: an evidence-based review. Am J Obstet Gynecol. 2006;195:673-689. 

5. Andrews JI, Shamshirsaz AA, Diekema DJ. Nonmenstrual toxic shock syndrome due to methicillin-resistant staphylococcus aureus. Obstet Gynecol. 2008;112:933-938. 

6. deMoya MA, del Carmen MG, Allain RM, Hirschberg RE, Sephard JO, Kradin RL. Case 33-2009: A 35-year-old woman with fever, abdominal pain, and hypotension after cesarean section. N Engl J Med. 2009;361:1689-1697. 

7. Cohen AL, Bhatnagar J, Reagan S, et al. Toxic shock associated with Clostridium sordellii and Clostridium perfringens after medical and spontaneous abortion. Obstet Gynecol. 2007;110:1027-1033. 

8. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368-1377. 

9. Russel JA. Management of sepsis. N Engl J Med. 2006;355:1699-1713. 

10. Sheffield JS. Sepsis and septic shock in pregnancy. Crit Care Clin. 2004;20:651-660.

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