Anesthesiology

The Infected Parturient

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What the Anesthesiologist Should Know before the Operative Procedure

Infection is the second leading cause of pregnancy-related mortality in the United States (13.6% for 2006-2010). Unlike post-partum hemorrhage and hypertensive disorders of pregnancy, mortality from infections has not decreased over the past decades.

It is imperative that the anesthesiologist know the source of infection, the infecting agent, and whether treatment has been instituted. In addition, it is important to know the planned procedure, the reasons for the procedure, and the urgency – that is, is there time to begin treatment prior to induction of anesthesia?

The anesthesiologist will want to know if the infection is localized or systemic and the hemodynamic, metabolic, respiratory, and coagulation effects that the infection has on the parturient. Infections occurring in the urinary tract, pulmonary, and other organ systems, can occur during pregnancy. For laboring women, the most common infection is chorioamnionitis.

The most common procedure in infected parturients remains vaginal or cesarean delivery. Regional analgesia or anesthesia is appropriate in most cases. The usual contraindications to regional analgesia / anesthesia will apply: coagulopathy, local infection at the site of needle placement, hemodynamic instability, mental status change (i.e., is the patient uncooperative), or patient refusal.

In patients with severe chorioamnionitis, uterine atony may complicate the postpartum period and may necessitate procedures to control it, ranging from hypogastric or uterine artery ligation, B-Lynch sutures, radiographic embolization, to hysterectomy.

The determinants of anesthetic approach will be the hemodynamic and mental status of the patient, whether the infection is local or systemic, whether the patient is septic, whether antibiotic treatment has started, and the respiratory status (e.g., whether the parturient’s spontaneous ventilation and oxygenation has been compromised from the primary infection or secondary effects of infection and sepsis, such as acute respiratory distress syndrome [ARDS]).

What is the risk of delay in order to obtain additional preoperative information?

Timing of delivery or other procedure is dependent on the reasons for the operative procedure.

Emergent: Patients can usually benefit from temporary optimization before surgery. Surgery is rarely an emergency in the setting of hemodynamic instability from sepsis.

Urgent: For mothers with HIV infection, cesarean delivery should be performed as soon as proper antiviral treatment is completed. Urgent cesarean delivery in these situations aims to minimize the risk of vertical viral transmission to the fetus / neonate.

With prolonged rupture of membranes and chorioamnionitis, delivery should be completed as soon as possible.

Neuraxial analgesia / anesthesia can be safely provided with the above infectious situations.

Neuraxial analgesia / anesthesia should be avoided in patients with untreated bacteremia and sepsis.

2. Preoperative evaluation

Although sepsis is relatively uncommon among parturients, it carries a significant case fatality – up to 30% of maternal deaths are caused by or associated with sepsis. Sepsis has a significant impact on the anesthetic management due to marked hemodynamic instability as well as multi-organ system involvement.

Escherichia coli is associated with both antepartum and puerperal sepsis, whereas group B streptococcus most often with intrapartum sepsis. Chorioamnionitis is the most common infection in the parturient, occurring in about 1% of patients. It may be associated with transient bacteremia or severe sepsis if left untreated, but is generally a localized rather than systemic infection and responds well to antibiotics and delivery. Dystocia, prolonged labor and post-partum hemorrhage due to uterine atony can complicate chorioamnionitis.

Due to physiologic changes associated with pregnancy, asymptomatic bacteriuria and lower urinary tract infection carry a 20-30% increased risk of developing pyelonephritis in parturients, leading to maternal and fetal complications, including preterm labor. Like chorioamnionitis, if left untreated, pyelonephritis can progress to sepsis.

HIV infection may be common in some locations and patient population groups. If diagnosed prior to pregnancy, these patients are often on an aggressive antiretroviral medication regimen and are not likely to have advanced multi-organ system involvement. Scheduled cesarean delivery should be performed before onset of labor and rupture of membranes, typically as soon as a zidovudine infusion is completed, to reduce the risk of vertical transmission to the neonate. Vaginal delivery may be an option if the viral load is less than 1000 copies/mL.

  • Medically unstable conditions warranting further evaluation include: Infectious complications that may have a significant medical impact on organ function: CNS dysfunction and encephalitis, advanced stage hepatitis, pneumonia, ARDS, coagulopathy either as a primary effect of infections (e.g., hemorrhagic fever associated with hanta virus), secondary to hepatic failure or disseminated intravascular coagulation (DIC), or hemodynamic instability from sepsis requiring vasopressor support.

  • Delaying surgery may be indicated if there is significant organ dysfunction secondary to viral or bacterial infection that would require stabilization or optimization prior to surgery. The most common example is dehydration as a result of vomiting/diarrhea. Others would include sepsis, pneumonia or ARDS, increased ICP resulting from encephalitis, severe coagulopathy resulting from hepatic failure, or cardiac dysfunction secondary to myocarditis or valvular dysfunction. It is important to understand that in certain circumstances such as rapidly deteriorating fetal acid/base status or maternal bleeding, delay may not be possible.

3. What are the implications of co-existing disease on perioperative care?

I. Perioperative evaluation: Perioperative evaluation should focus on the location and causative agent of infection, if known, and the impact that the infection may have on organ function. Isolated infections will have little impact on anesthesia decision making unless there is a possibility of bacteremia or viremia. In the case of bacteremia, a single course of antibiotics will allow for regional anesthesia in most cases.

In the case of viremia, many experts would recommend that spinal anesthesia be avoided for fear of subsequent viral encephalitis or meningitis. Little data is available, however. It should be noted that in the absence of dural puncture, the likelihood of spreading virus particles into the CNS is very rare. In this case, epidural analgesia/anesthesia could still be considered.

Regional anesthesia is not contraindicated in patients with HIV infections that are stable. In most cases, CNS involvement occurs early in the course of HIV infection, even in the absence of symptoms. As primary herpes simplex viruses type 2 (HSV-2) infections are more frequently associated with viremia than secondary HSV-2 infections, regional anesthesia should be weighed against risks and benefits of general anesthesia in women with primary infections whereas it is usually safe in women with secondary infections. Examine the patient for lesions at or near the site of anticipated needle placement if a neuraxial regional analgesic/anesthetic is planned. Risk factors for regional anesthesia must be weighed against the risks of general anesthesia.

Examine the patient's airway, and determine NPO, hemodynamic, volume status, and organ function status. Although bacterial or viral seeding from neuraxial blocks is extremely rare, general anesthesia may be considered if there is significant hemodynamic instability, coagulopathy, or mental status change.

II. Patients should be assessed for systemic infections and associated complications to determine the anesthetic approach. Look for clinical and laboratory evidence of coagulopathy. Look for evidence of ongoing infection: fever, malaise, lymphadenopathy. Obtain the results of blood cultures, if available.

III. Currently, there are no separate diagnostic criteria for sepsis in pregnancy. The Surviving Sepsis Campaign Committee outlined diagnostic criteria for sepsis and severe sepsis.

Sepsis: a documented or suspected infection, with some of the following: fever >38.3°C; hypothermia (<36°C); tachypnea; altered mental status; significant edema or positive fluid balance (>20 mL/kg over 24 hrs); hyperglycemia (plasma glucose >120 mg/dL) in the absence of diabetes; leukocytosis (WBC >12,000 µL-1); leukopenia (WBC <4,000 µL-1); normal WBC with >10% immature forms; plasma C-reactive protein >2 SD above normal; plasma procalcitonin >2 SD above normal value; arterial hypotension (SBP <90 mmHg, MAP <70 mmHg, or SBP decrease >40 mmHg); SvO2 >70%; cardiac index >3.5 L/min/M2; arterial hypoxemia (PaO2/FiO2 <300); oliguria (urine output <0.5 mL/kg/hr); creatinine increase >0.5 mg/dL; coagulation abnormalities (INR >1.5 or aPPT >60); thrombocytopenia (<100,000 µL-1); hyperbilirubinemia; hyperlactatemia (>1 mmol/L); decreased capillary refill. Severe sepsis is defined as sepsis plus evidence of organ dysfunction: hypoperfusion, or hypotension, lactic acidosis, or oliguria. Septic shock is sepsis with hypotension despite adequate fluid resuscitation.

Effective treatment of sepsis relies on early recognition based on these variables. Delayed recognition is a key contributor to the mortality. There have been several modified early warning scoring systems (MEWS) and modified obstetric early warning scoring systems (MOEWS). These systems use common sepsis variables (pulse, blood pressure, respiratory rate, temperature, O2 saturation, and mental status) and sets different color-coded (amber, red) alert limits and trigger scores. Due to physiological changes associated with pregnancy, which can mimic or overlap the diagnostic criteria for sepsis and the scoring alerts, most of these systems do not predict sepsis well in parturients, and tend to over-predicting sepsis. A Sepsis in Obstetrics (SOS) model has been used to predict ICU admission, with a higher positive predictive value than MEWS.

IV. Perioperative risk reduction strategies: Early communication among anesthesia, obstetric, and infectious disease, and critical care teams is imperative for good outcome. The presence of bacteremia or viremia should be determined when possible. Antibiotics, antiviral, and antiretroviral agents should be initiated or continued. For patients in labor, frequent evaluation of coagulation status should be done if coagulopathy from infection is anticipated. Patients who are dehydrated (e.g., from nausea and vomiting) should continue to be administered fluids if ongoing dehydration is anticipated.

a. Cardiovascular system

i. Acute/unstable conditions: Due to volume status change with pregnancy, cardiovascular derangements may not occur unless the patient is severely septic. In sepsis, the patient may exhibit an exaggeration of the normal physiologic changes associated with pregnancy (i.e. increased cardiac output and decreased systemic vascular resistance). Cardiac output may increase 50% over non-pregnant values and systemic vascular resistance normally decreases 20% from non-pregnant values. Direct arterial blood pressure monitoring and central pressure monitoring may be indicated. An echocardiogram will be helpful in assessing the volume status, myocardial contractility, and presence of pericardial effusion. Echocardiography and ECG may also be indicated if the diagnosis of endocarditis is entertained or the patient is suffering from some form of parasitic disease (e.g., Chagas disease).

ii. Baseline coronary artery disease or cardiac dysfunction – goals of management: In cases of infections with specific cardiac implications (e.g., endocarditis or Chagas disease), treatment should be directed at the causative organism.

In patients with sepsis, goals of treatment should be directed at maintaining adequate tissue perfusion. The mean arterial pressure (MAP) should be maintained at 65 mmHg or 70 mmHg or higher or increased if fetal acid-base status is deteriorating. The first goal is to administer fluids (colloid or crystalloid) to achieve a CVP between 8 and 12 mmHg with an initial infusion of 20 mL/kg crystalloid or colloid equivalent. Vasopressors should be initiated if hypotension continues despite adequate fluid administration. Inotropes may be indicated if there is evidence of myocardial dysfunction. Some specific infections, such as Dengue shock syndrome or cholera, require aggressive fluid administration.

b. Pulmonary

i. COPD

Multiple organisms can cause infection that may have an impact on pulmonary function. Some of the more unusual causes of pneumonia are varicella-zoster virus (chickenpox), rubeola (measles), hantavirus pulmonary syndrome, Leptospirosis, TB, schistosomiasis and chlamydia.

ARDS is a common complication of sepsis and may require intubation and mechanical ventilation. In these cases, optimal oxygenation and peripheral O2 delivery and consumption are imperative. These can be monitored with ABGs, SaO2, SvO2, and lactate levels. Remember that during pregnancy, normal values for PaO2 range from 103 to 107 mmHg at sea level. The normal value for PaCO2 is 30 to 32 mmHg. Normal arterial pH increases to 7.44. HCO3- decreases to about 20 mEq/mL to compensate for normally occurring, modest respiratory alkalosis.

ii. Reactive airway disease (asthma)

Asthma can be induced or aggravated by respiratory tract infections. Antibiotics and beta-adrenergic inhalers are usually safe during pregnancy. Regional anesthesia offers the advantage of avoiding stimulating the reactive airway. General anesthesia may be necessary if the patient is unstable and requires accessory muscles for respiration. Prostaglandin-based uterotonic agents are relatively contraindicated as they may cause or exacerbate bronchospasm.

c. Renal-GI:

Gastroenteritis can cause sufficient nausea, vomiting, and diarrhea, leading to significant dehydration. Vibrio cholera infections can lead to severe dehydration. Prior to any surgical intervention, fluid replacement should be initiated in patients who may be dehydrated from nausea, vomiting, and diarrhea. Varicella zoster infections may be complicated by hepatitis, pancreatitis, and nephritis. Yellow fever may lead to hepatorenal syndrome. Leptospirosis may involve the liver and kidney and lead to hepatorenal syndrome as well. Trypanosoma cruzi (Chagas disease) can cause dysphagia, constipation, GERD, megacolon, and megaesophagus.

The intestinal tract is at risk for developing ischemia during sepsis and septic shock. This causes mucosal injury and increased permeability allowing translocation of bacteria and endotoxins, further worsening SIRS and contributing to multi-organ dysfunction. Hypovolemia may also lead to acute renal failure in the face of systemic hypoperfusion.

d. Neurologic:

Multiple infectious agents can lead to or be complicated by meningitis and/or encephalitis. HIV can involve the CNS early in the course of the disease but may be asymptomatic in the early stages. HIV may be complicated by a peripheral neuropathy as well. HSP-2 may lead to encephalitis as can varicella-zoster infections, leptospirosis, TB, and typhoid fever. Typhoid fever, in particular, may be complicated with meningitis, cerebral edema, and brain and epidural abscesses. Late-stage syphilis may involve the central and peripheral nervous systems. Severe sepsis and septic shock may be associated with mental status changes. General anesthesia is preferred for surgery in presence of a mental status change.

d. Endocrine:

Patients with diabetes are likely to have increased insulin requirements in the face of infection and fever. Hypoglycemia may complicate varicella-zoster infections. Sepsis involves a catabolic response with insulin resistance, and glucose should be closely monitored and managed. Therapy should be directed at maintaining glucose levels from just above the lower limits of normal to below 150 mL/dL.

f. Additional systems/conditions that may be of concern:

Primary hepatitis (e.g., A, B, and C), tissue injury from infections and sepsis, as well as complications caused by other infectious agents, may lead to coagulopathies that need to be identified and corrected prior to cesarean delivery or neuraxial analgesia for vaginal delivery.

4. What are the patient's medications and how should they be managed in the perioperative period?

Antibiotics and antivirals should be continued preoperatively, intraoperatively, and postoperatively if indicated.

g. Are there medications commonly seen in patients undergoing this procedure and for which should there be greater concern?

i. This may include medications specific to diseases associated with surgery. Common antibiotics used in infected parturients are likely to be penicillin and penicillin derivatives, cephalosporins, clindamycin, gentamicin, and vancomycin. Aminoglycosides can prolong the effect of nondepolarizing muscle relaxants. Protease inhibitors used to treat HIV inhibit cytochrome P-450, which can prolong the effects of benzodiazepines and opioids.

ii. Patients suffering from severe sepsis or septic shock may be on glucocorticoids and, therefore, may need stress doses of glucocorticoids perioperatively.

h. What should be recommended with regard to continuation of medications taken chronically?

All antibiotics and antivirals should be continued in infected parturients presenting for labor and delivery. Cesarean delivery for women with HIV is to be performed as soon as therapy with zidovudine is completed.

i. How to modify care for patients with known allergies

Antibiotics and antivirals will need to be altered for patients with known allergies to specific agents or class of drugs. For patients with true allergy to penicillin, clindamycin or vancomycin is often substituted.

k. Does the patient have a history of allergy or adverse reaction to anesthesia drugs?

  • Local anesthetics/muscle relaxants: Allergy to the ester class of local anesthetics is more common than allergy to the amide class. If a patient is allergic to an ester, then an amide may be substituted. Cross reactivity among the individual amide local anesthetics is extraordinarily rare, if it exists at all.

  • In patients with severe infections, succinylcholine may cause life-threatening hyperkalemia.

  • History of malignant hyperthermia should be inquired.

5. What laboratory tests should be obtained and has everything been reviewed?

Laboratory confirmation of the causative agent should be sought whenever possible. This would include cultures taken at the site of infection as well as blood cultures, preferably before antimicrobial treatment is started.

Baseline hemoglobin levels should be obtained when there is concern for infection in the parturient, but in cases where the specific infection is causing a hemorrhagic disorder, hemoglobin levels should be followed closely. Hantavirus, dengue fever, yellow fever, and leptospirosis are known to lead to hemorrhagic disorders. Any infection causing or complicated by multisystem organ failure can be associated with thrombocytopenia and DIC.

Liver function tests should be obtained if liver involvement is suspected.

Coagulation studies must be obtained in cases where liver failure may complicate the infection, or DIC is suspected from consumptive coagulopathy arising from tissue injury secondary to infections. Coagulation status can also be monitored with thromboelastometry.

Arterial blood gases (ABGs) should be obtained in patients suffering from ARDS from sepsis and multi-organ dysfunction, or pulmonary infections, including TB, viral and bacterial pneumonias.

Type and screen are commonly obtained as a matter of routine in patients undergoing cesarean delivery, but if excessive bleeding is anticipated because of on-going coagulopathy, then obtaining a type and cross match for blood and blood products would be wise.

  • Hemoglobin levels: Pregnant patients have a dilutional anemia. Hemoglobin levels as low as 10 g/dL are not considered abnormal. Normal, healthy pregnant patients in labor can have elevated white blood cell counts.

  • Electrolytes:A low BUN is normal in healthy parturients. The upper limit of normal for serum creatinine is 0.7 g/dL in normal, healthy parturients.

  • Coagulation panel and thromboelastometry: Virtually all clotting factors are elevated in normal-term pregnant patients.

Intraoperative Management: What are the options for anesthetic management and how do I determine the best technique?

Regional analgesia/anesthesia has been the mainstay of obstetric anesthesia for decades. For labor and delivery, epidural analgesia provides the most effective pain relief with the least amount of sedation of the mother or newborn. For cesarean delivery, regional anesthesia is preferred for a variety of reasons, the most important being avoidance of a difficult airway, which is more common among obstetric patients than among non-pregnant patients.

Neuraxial anesthesia

a. Benefits: Neuraxial analgesia for labor provides superior pain relief and less sedation and fetal effects compared to intravenous or inhalational agents. Neuraxial analgesia/anesthesia for vaginal or cesarean delivery allows for an awake participatory parturient. Neuraxial anesthesia for cesarean delivery avoids the risks of general anesthesia, promotes skin-to-skin contact, and gives an opportunity to provide postoperative regional analgesia. The term parturient is at particular risk of a difficult airway and aspiration, and the level of difficulty increases as the labor progresses.

b. Drawbacks:Many anesthesiologists may be concerned about the risk of spreading infective organisms into the CNS when performing epidural or subarachnoid analgesia/anesthesia. There are no studies confirming such risks in the parturient with low grades of bacteremia or viremia. If infection is localized, there are no infectious risks to neuraxial techniques, unless the infection is at the site of needle and catheter entry. In the patient with systemic infection, it is appropriate to provide neuraxial analgesia/anesthesia if the patient had received appropriate antibiotics and has begun to defervesce. Patients who show signs of systemic infection following placement of an epidural catheter or subarachnoid block are not at increased risk for CNS infection, and should not have an already existing epidural catheter removed simply because the patient may be bacteremic.

c. Patients with HIV who are receiving treatment are not at risk of spreading HIV to the CNS. This includes patients who are in need of an epidural blood patch. Most patients who will ultimately go on to have CNS complications of HIV already had CNS infection early in the course of disease even if they were asymptomatic.

d. Patients with primary HSV-2 infection with evidence of systemic disease and viremia should probably avoid regional analgesia/anesthesia because of the theoretical risk of spreading the disease into the CNS. However, it may be difficult to recognize the primary infection that will appear like other severe viremic illnesses. Culture results may not be available for some time. There are no studies, however, linking neuraxial analgesia/anesthesia with CNS involvement in patients with primary HSV-2 infection and viremia. The decision to use regional analgesia/anesthesia in these patients should be individualized and the risks of alternatives (e.g., general anesthesia in a patient with a difficult airway) should be considered. Secondary infection with localized lesions is not a contraindication to neuraxial anesthetics.

e. Patients who are in septic shock are generally not candidates for regional anesthesia, as they are hemodynamically and mentally unstable.

General anesthesia

a. Benefits: General anesthesia is a reliable and effective technique. In cases of severe sepsis and/or multi-system organ failure with hemodynamic instability, general anesthesia is associated with less vasodilation. General anesthesia is also appropriate for patients with severe pulmonary complications of sepsis such as ARDS, allowing higher airway pressure and PEEP to reduce shunt fraction. Patients with pulmonary infections who require use of accessory muscles of respiration may also benefit from positive pressure ventilation with reduced work of breathing. General anesthesia is also chosen when there is on-going coagulopathy that cannot be corrected in time for surgery. As indicated above, patients with bacteremia and sepsis who are not responding to antibiotics may be better managed with general anesthesia. Although there are no studies to support general anesthesia over regional anesthesia among patients with systemic viral diseases and associated viremia (e.g., HSV-2 and varicella-zoster), general anesthesia may be a reasonable option.

b. Drawbacks: General anesthesia in the parturient does not allow for an awake participating patient. Obstetric patients are at increased risk of airway difficulties and aspiration. In addition, airway manipulation in patients with early-onset pulmonary complications may increase the risk of worsening the disease.

c. General anesthesia is not an option for labor and vaginal delivery.

6. What is the author's preferred method of anesthesia technique and why?

Regional anesthesia is the preferred technique for cesarean delivery. Neuraxial analgesia for labor and delivery (spinal, epidural, or combined spinal-epidural) is the most effective form of pain management with the least degree of sedation. Unless there are absolute contraindications to neuraxial analgesia/anesthesia, this is the favored approach.

Absolute contraindications include hemodynamic instability, coagulopathy, severe sepsis, localized infection at the site of needle puncture, and patient refusal or lack of cooperation. Outside of these contraindications, all factors discussed above should be considered before an anesthetic technique is chosen in the infected parturient.

a. Neurologic:

N/A

b. If the patient is intubated, are there any special criteria for extubation?

Extubation criteria for parturients are similar to the general population. Patients who are septic with hemodynamic instability or severe pulmonary dysfunction may need to remain intubated if general anesthesia has been used.

c. Postoperative management

What analgesic modalities can I implement?

Patients who have had neuraxial anesthesia can be given preservative-free morphine, either intrathecally at the time of subarachnoid block or during surgery or immediately postoperatively in the patient with an epidural catheter. Neuraxially administered morphine may be associated with recurrence of oral HSV-1 in the susceptible patient. The exact mechanism is unknown but may be related to facial scratching from pruritus that activated old lesions. It could also be related to immunologic modulation caused by morphine in the nucleus of the trigeminal nerve. Neuraxial morphine does not lead to recurrence of genital HSV-2 lesions. In patients who receive general anesthesia, patient-controlled analgesia can be administered as long as the patient is alert and awake postoperatively.

What bed acuity level is appropriate?

Patients who have had regional anesthesia but are likely to become unstable postoperatively may need to recover in an ICU or monitored bed setting. Patients whose infection was complicated by coagulopathy may be at risk for continued bleeding and may need reoperation. In these cases, it is wise to maintain adequate IV access. If central IV access has been used either for fluid and blood administration or for central monitoring, this should be continued until the patient is stable.

What are common postoperative complications and ways to prevent and treat them?

Patients who are debilitated from infection or complications of infection may be at increased risk for venous or pulmonary thromboembolism. The patients are often placed on unfractionated heparin or low molecular-weight heparin. Sequential compressing devices on lower extremities are also used. If the patient has a continued epidural catheter or has had a single-injection regional anesthetic, then guidelines published by the American Society of Regional Anesthesia (ASRA) should be followed.

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