Infection and Fever in Pregnancy

Wenonah Linette Wood, University of California San Diego, USA

Introduction
Infection remains the leading cause of morbidity and mortality worldwide. ! and "# $he severity and course of infection de%end on a variety of factors, including the virulence of the strain of infecting organism, the immune res%onse of infected host, and available treatment modalities. Infection is the most common cause of fever, reflecting the effect of %yrogens on the hy%othalamus. !# &ever is a common clinical %roblem in labor and delivery suites' a febrile %arturient may %ose a diagnostic dilemma and thera%eutic challenge to both an obstetrician and an anesthesiologist involved in her %eri%artum care. &ever can result from a variety of infectious microorganisms (Table 1 and Table 2), tissue trauma, malignancy, drug administration, and endocrine and immunologic disorders. $he infectious etiology of fever in a %arturient may be %regnancy*s%ecific, such as chorioamnionitis, or not s%ecific to %regnancy, such as urinary tract infection (U$I' Table 3).
$able !. +iruses ,ost Commonly -ncountered in .regnancy

$able ". /acterial Infections in .regnancy

$able 0. Infectious Disorders in the .arturient with Anesthetic Im%lications

1S+ 2 her%es sim%le3 virus' 1I+ 2 human immunodeficiency virus.

$he ris4 to the mother and the fetus is greatly increased in %regnancy that is com%licated by infection and fever. $he diverse clinical manifestations of various infectious disorders, combined with the uni5ue anesthetic im%lications of %regnancy, may result in life* threatening com%lications, significantly im%acting the %ractice of obstetrical anesthesia. 6egional anesthesia has become a hallmar4 of modern obstetric anesthesia %ractice and a %aramount techni5ue for labor analgesia. $he diagnosis of infection in %regnancy often raises 5uestions about the safety of regional anesthesia in febrile %atients. Des%ite this concern, and lac4 of universal guidelines, it has now been well established that the %resence of infection and fever in labor does not always %reclude the administration of neura3ial anesthesia. "# $he decision to administer regional anesthesia in a febrile %arturient should be based on an individual ris4*to*benefit ratio. $he 4nowledge of the underlying infectious %rocess, available treatment modality, and anesthetic im%lications of both are im%ortant for o%timal anesthetic management.

Fever: definition and pathophysiology

7ormal body function de%ends on a relatively constant body tem%erature (with normal diurnal variations), which is regulated by the hy%othalamus and determined by the balance between heat %roduction and heat loss to the environment. 0# $he core tem%erature (rectal, eso%hageal) is usually 8.9:C higher than the oral tem%erature. $here is a circadian fluctuation in tem%erature with the nadir at ; A, and the %ea4 at < .,. In females there is a monthly cycle during which the tem%erature increases at the time of ovulation and falls bac4 to baseline at the onset of menstruation. $he normal core body tem%erature in adults ranges from 0;.9:C to 0<:C. 0# $he human body has a set %oint tem%erature and tem%erature control mechanisms that constantly ad=ust body tem%erature to maintain this level. &ever is an increase in core body tem%erature above 0<:C mediated by endogenous %yrogens, which is secondary to an increase in the hy%othalamic set %oint. !, 0, > and 9# $he human body tem%erature

rarely e3ceeds >!:C. 7ormal circadian fluctuation in body tem%erature with increase in the evening and decrease in the morning continues, even in febrile %atients. ;# Under normal circumstances, core body tem%erature is tightly regulated, with a variation of a%%ro3imately 8.9:C. Although the benefits of fever are uncertain, it has been suggested that the increased body tem%erature aids in the activation of the host immune res%onse, with augmentation of bactericidal, %hagocytic, and chemotactic %ro%erties of %olymor%honuclear leu4ocytes. $he negative as%ects of fever include increased basal metabolic rate and increased cardiac demand.

Interaction with pregnancy

.regnancy is associated with an increase in the maternal basal metabolic rate. ?# $he %ain of labor causes the %arturient to hy%erventilate, which, along with accom%anying %ers%iration, leads to com%ensatory heat dissi%ation. ,aternal body tem%erature in labor is also significantly affected by the degree of %hysical activity. 1igher tem%eratures have been re%orted in laboring %arturients who remained calm and inactive. <# &etal tem%erature is a%%ro3imately 8.9:C higher than maternal tem%erature. $he maternal*fetal tem%erature gradient closely correlates with utero%lacental blood flow and fetal o3ygen delivery. 1y%erthermia (defined as an increase in core body tem%erature above 0<:C) in a laboring %atient results in higher maternal o3ygen consum%tion and decrease in fetal o3ygen delivery. ? and <# ,aternal infection in labor is associated with increased %erinatal morbidity. @# $he anatomical changes associated with %regnancy may %redis%ose women to certain infections. Urinary tract dilation is one of the most significant alterations induced by %regnancy. $hese changes are mediated by hormonal (%rogesterone) and mechanical factors, resulting in urinary stasis and %redilection to U$Is. It is estimated that the incidence of %yelone%hritis in %regnancy is a%%ro3imately !A. @# .regnancy is associated with decreased immune system function. " and @# Some febrile diseases may, therefore, ta4e a more severe course in %regnancy leading to trans%lacental transmission of infectious agent and fetal =eo%ardy. $he source of fever should be identified and %ossible fetal im%lications considered. U%%er res%iratory or U$Is, for e3am%le, are less li4ely to %ose a significant danger to the fetus as com%ared with human immunodeficiency virus (1I+) infection or chorioamnionitis. $he %ossibility of %eri%artum transmission of infectious microorganisms will affect the obstetric and subse5uent anesthetic management of these %atients (e.g., %erforming an abdominal delivery in an 1I+*infected %arturient). $he overall incidence of maternal infection in labor is estimated to be 0.!A.B .resence of bacteria in blood sam%les alone (unassociated with fever andCor infection), obtained from %arturients, seems 5uite common. It has been determined that even routine %rocedures in labor, such as insertion of a urinary catheter, may result in transient bacteremia. 1owever, the clinical significance of these findings and anesthetic im%lications remain unclear. Animal studies have found evidence to suggest that bacteremia may increase the ris4 of meningitis after subarachnoid bloc4. !8# $he e3tra%olation of these data to humans is 5uestionable and the im%ortance to clinical %ractice uncertain.

Viral infections in pregnancy

+iruses most commonly encountered in %arturients include influenDa virus, her%es sim%le3 virus (1S+), he%atitis viruses, cytomegalovirus (C,+), %a%illomavirus, and 1I+ (Table 1). Additionally, febrile diseases caused by measles, rubella, and chic4en%o3 viruses may a%%ear during %regnancy.

Herpes simplex virus

General considerations
1er%es sim%le3 virus is a double*stranded deo3yribonucleic acid (D7A) virus. It belongs to a large grou% of double*stranded D7A viruses, which also encom%asses varicella* Doster virus, C,+, and -%stein*/arr virus. $wo ty%es of 1S+ have been identified. 1er%es sim%le3 virus ty%e ! is generally associated with oral lesions (cold sores) and transmission occurs through oral secretions. 1er%es sim%le3 virus ty%e " is associated with %ainful vesicular or %a%ular lesions on mucous membranes or s4in of the genital tract. Se3ual contact remains the %redominant mode of 1S+ ty%e " transmission. /oth ty%es of 1S+ share the %ro%erty of asym%tomatic %eriods of latency interru%ted by e%isodes of reactivation. During %eriods of latency the virus resides in the sensory neural ganglia. !!# $wo cases of %ost%artum 1S+ endometritis have been re%orted in the literature. /oth infants died from disseminated 1S+ infection. !"#

Anesthetic management
Differentiation between the %rimary (initial) and secondary (recurring) infection is of critical im%ortance before the administration of anesthesia. Unfortunately, such a distinction often %roves very difficult in clinical settings. !0# $he administration of regional anesthesia often raises concerns about neura3ial s%read of the virus and %ossibility of a disseminated disease. Such concern seems more li4ely in %rimary infections with transient %resence of the virus in the systemic circulation. !0# $he transient viremia of %rimary infection is followed by %ermanent antibody %roduction > to ; wee4s later. $he coe3istence of ty%ical genital lesions with systemic sym%toms (fever, myalgia, and headache) usually suggests a %rimary infection' however, a%%ro3imately 08A of these %atients remain asym%tomatic. $he lac4 of sym%toms may additionally cloud the differential diagnosis. !># When %rimary infection is ac5uired in the %eri%artum %eriod, the ris4 of vertical transmission to the neonate is very high because of the %resence of viremia. !9# $o date, the safety of regional anesthesia in %rimary infection with 1S+ has not been established. In contrast, viremia is rarely %resent in %atients with secondary, recurrent 1S+ ty%e " infection, and several investigators have documented safety of regional anesthesia in these %atients. !;, !? and !<# 1owever, the %resence of active lesion at the site of needle insertion obviously would %reclude regional anesthesia in both grou%s of %atients. -%idural analgesia utiliDing o%ioids, %articularly mor%hine, has been sus%ected of reactivation of 1S+*! lesions in the thoracic and %erioral locations. !@ and "8# Similar findings have been re%orted with subarachnoid o%ioids. , E $he %atho%hysiology of this

reactivation remains obscure, although %ruritus, scratching, and activation of the nucleus of the fifth cranial nerve by o%ioid binding, have been %ostulated. "! and ""# $his association, however, has not been confirmed by other researchers and remains controversial. "0# It is noteworthy that no such association has been re%orted between neura3ial o%ioids and recurrence of 1S+ ty%e " infections.

Hepatitis
General considerations
+iral he%atitis results from infection by a s%ectrum of viruses, which may vary in the mode of transmission and clinical e3%ression. 1e%atitis viruses ty%e A, /, C, D, and have been identified. $he onset of the disease may be gradual or fulminant. $he incubation %eriod and seroconversion may vary from " to "> wee4s. "># $he clinical sym%tomatology may include fever, anore3ia, fatigue, nausea, vomiting, abdominal discomfort, and =aundice. $here is little sur%rise that some of these sym%toms might draw insufficient attention since their occurrence in otherwise normal %regnancy is common. "9#

Anesthetic management
Although mild he%atitis does not significantly alter anesthetic management and %regnancy outcome, careful %reanesthetic evaluation should determine the degree of he%atic im%airment. Laboratory evaluation should include serum electrolytes, creatinine, blood urea nitrogen, bilirubin, transaminases, al4aline %hos%hatase, albumin, and %rothrombin time. Whenever %ossible, maternal serum should be chec4ed for the %resence of he%atitis / surface antigen (1bsAg). If a %regnant %atient with acute viral he%atitis must undergo emergency delivery, %rom%t correction of electrolyte abnormalities and dehydration is recommended. " and "9# If general anesthesia is selected, anesthetic drugs with 4nown e3trahe%atic metabolism are recommended. Standard doses of intravenous (I+) induction drugs are generally used because their action is terminated by redistribution rather than metabolism or e3cretion. Isoflurane remains the %otent inhaled volatile anesthetic of choice because it has the least effect on he%atic blood flow. &actors such as hy%otension, e3cessive sym%athetic stimulation, and high airway %ressure should be avoided because they are causes of reduced he%atic blood flow. 6egional anesthesia may be safely em%loyed in febrile %arturients with viral he%atitis %rovided thrombocyto%enia is absent, coagulation studies remain normal, and hy%otension is avoided. /ecause history of I+ drug abuse and coe3isting 1I+ infection are common, combative behavior, widely fluctuating mood level, and altered %ain %erce%tion may be encountered when regional anesthesia is selected for these %atients. ";# $he ris4 of vertical transmission of he%atitis C to the fetus is significantly increased %eri%artum. "?# Universal safety %recautions are recommended when handling blood and bodily fluids from these %atients.

Human immunodeficiency virus

General considerations
$he ac5uired immune deficiency syndrome (AIDS) has grown from negligible numbers in !@<! to a cumulative total of nearly @ million cases, as re%orted by the World 1ealth FrganiDation as of !@@?. "<# In the year "88!, it was estimated that over 0" million individuals worldwide were infected with 1I+Gthe vast ma=ority of whom live in the develo%ing world. "<, "@ and 08# In the United States, women have been identified as the fastest growing grou% of new AIDS %atients. "@# Conse5uently, it is not uncommon to find %regnant women who are 1I+*%ositive. "<, "@ and 08# -arly identification of 1I+ infection in %regnancy is of the utmost im%ortance. Unfortunately, few %hysicians (both obstetricians and anesthesiologists) in5uire about the %ossibility of 1I+ infection when interviewing their %atients. 0!# $he 1I+*%ositive %atient, regardless of her clinical condition, meets the criteria for AIDS, by definition, when the CD>H $ cell count falls below "88 cellsCmL. 0!# 1igh maternal viral load increases the li4elihood of %erinatal transmission of 1I+. 0" and 00# Clinical evidence suggests that most %erinatal 1I+ transmissions occur during labor and delivery. 0>, 09 and 0;# Iind et al. 0?# studied the effect of elective cesarean section and Didovudine %ro%hyla3is on vertical 1I+ transmission, and they concluded that elective cesarean section and Didovudine %ro%hyla3is a%%ear to have an additive effect in the %revention of vertical 1I+ transmission. /ecause of these recent findings, many 1I+* %ositive women are being advised to undergo elective cesarean section. 0?#

Anesthetic management
$he diagnosis of 1I+ infection in %regnancy often raises 5uestions about the safety of regional analgesia in these %atients. 0<# $his controversy first began when it was suggested that the introduction of a s%inal needle into the 1I+ %atient would s%read the disease into the central nervous system (C7S) and, therefore, increase the %atientJs ris4 for develo%ment of the neurologic se5uelae of this disease. 0@# It is now well established that 1I+ infection does not %reclude the administration of regional anesthesia. 0< and 0@# 1I+ is a neurotro%ic virus and C7S infection ta4es %lace early in the course of the disease %rocess. 0<, >8 and >!# 7eurotro%ic %redis%osition of an 1I+ virus is res%onsible for sym%toms of neurologic dysfunction manifested clinically at the time of initial AIDS diagnosis in u% to >8A of infected %atients. >!# 1I+ sero%ositivity alone should not determine the %referred method of anesthesia. Anesthetic management of these %atients must, therefore, be tailored to the individual obstetric indications, urgency and route of delivery, and %resence of coe3isting disease. Careful %hysical e3amination and documentation of neurologic deficits should be underta4en before induction of anesthesia. A significant number of 1I+*infected %atients have a %ast medical andCor social history that has in some way contributed to infection with 1I+. Substance abuse (I+ drug abuse in %articular) remains a significant ris4 factor and may have anesthetic im%lications. 0># $he coe3istence of other se3ually transmitted diseases such as he%atitis / and sy%hilis may be encountered. 0>#

Involvement of the res%iratory system with oro%haryngeal and eso%hageal %athology may render 1I+*infected %atients increasingly %rone to regurgitation, difficult intubation, and as%iration. F%%ortunistic %ulmonary infections may necessitate %rolonged mechanical ventilation in the %osto%erative %eriod. Careful e3aminations of the cardiovascular (subclinical cardiomyo%athy), renal (ne%hro%athy), and hematological (neutro%enia, thrombocyto%enia) systems are indicated in %reanesthetic assessment of these %atients. .atients with AIDS may e3hibit electrolyte disturbances, such as hy%onatremia, which may be due to adrenal infection by C,+ or mycobacteria. If severe, these disturbances should be corrected before induction of anesthesia. Although thrombocyto%enia may occur in the 1I+*%ositive %atient, it is rare for the %latelet count to be low enough as to im%act on the choice of anesthetic. 1owever, if the %latelet count decreases below 98,888Cmm, the ris4s of bleeding and e%idural hematoma may increase. >!# $reatment of com%lications of neura3ial anesthesia, including management of %ostdural %uncture headache (.D.1) should not differ from the standards of care for healthy %atients. S%ecifically, if .D.1 occurs, an e%idural blood %atch with autologous blood is safe and effective treatment in the 1I+*infected %atient >"# If general anesthesia is selected, dose ad=ustments for history of drug abuse (acute vs. chronic), com%romised he%atic and renal function, or generaliDed muscle wasting are necessary. 1I+*related %ulmonary %athology may re5uire a higher fraction of ins%ired o3ygen concentration. " and 0<# Increased sensitivity to o%ioids and benDodiaDe%ines has been re%orted in 1I+*infected %regnant %atients. Concern has been raised by some researchers that %otent volatile anesthetics also may de%ress the already com%romised immune system in 1I+*infected %atients. >0# $he ris4 of occu%ational e3%osure to infected blood and bodily fluids should never be underestimated when caring for these %atients. 7ecessary safety measures (universalCstandard %recautions) must be em%loyed when handling blood and blood %roducts of all %atients, not =ust those who are 4nown to be 1I+*%ositive., >># $here is a KwindowL of time between the %rimary 1I+ infection and seroconversion, during which the diagnosis can be delayed, yet viral transmission occur. $he use of gloves %revents @<A of an anesthesiologistJs contact with %atientJs blood and bodily fluids. , , >># $he ris4 of 1I+ transmission from a needle stic4 in=ury with 1I+*infected blood is a%%ro3imately 8.0"A. >9#

Bacterial infections in pregnancy

$he most common bacterial infections in %regnancy include U$Is, chorioamnionitis, res%iratory tract infections, and %ost%artum endometritis (Table 2). Systemic bacterial illness regardless of its origin may lead to serious maternal and fetal conse5uences if left untreated. $he incidence of maternal infection in labor is estimated to be 0.!A. , M Se%ticemia has been re%orted in 8.8?A of %regnant %atients. $he most common etiology is gram*negative organisms (@9A), with the remaining being caused by gram*%ositive and other bacteria. >;#

rinary tract infections

General considerations
Infections of the urinary tract are the most common bacterial infections encountered during %regnancy. Urinary tract infections include a s%ectrum of disorders ranging from asym%tomatic bacteriuria to %yelone%hritis. Asym%tomatic bacteriuria is diagnosed in a%%ro3imately !8A of %regnant women. ", >? and ><# $he incidence of %yelone%hritis in %regnancy has been estimated to be !A to "A. ><# .regnant women with acute %yelone%hritis re5uire %rom%t treatment. Cunningham et al. >@# suggested that acute %yelone%hritis during %regnancy may be associated with res%iratory tract infection and adult res%iratory distress syndrome (A6DS) leading to res%iratory failure. $he authors s%eculated that A6DS is caused by the %ermeability edema mediated by endoto3in* induced alveolar*ca%illary membrane in=ury. >@#

Anesthetic management
1emodynamic alterations may be %resent in a %arturient with acute %yelone%hritis, even in the absence of overt se%sis. ,ost %arturients with %yelone%hritis are dehydrated secondary to fever, vomiting, and anore3ia. >? and ><# $hese changes may lead to electrolyte imbalances, which should be corrected before administration of anesthesia. As%iration %ro%hyla3is is of the utmost im%ortance. Antibiotic thera%y is indicated before induction of regional anesthesia. $here is no evidence that regional anesthesia is detrimental in febrile %atients with U$I. "#

!horioamnionitis
General considerations
Chorioamnionitis, or acute intraamniotic infection, historically has been associated with maternal morbidity and mortality. 98 and 9!# $he incidence of intraamniotic infection in term %regnancy at delivery varies from 8.9A to !8.9A. 98# $he hallmar4 of the diagnosis is an increased maternal tem%erature of 0?.<:C or higher associated with uterine tenderness, foul*smelling amniotic fluid, and generaliDed sym%toms of infection. 9" and 90# ,aternal com%lications of chorioamnionitis include %ost%artum hemorrhage, %ost%artum infection, se%sis, and sometimes even death. Some investigations have suggested that chorioamnionitis may adversely affect uterine contractility leading to an increased incidence of cesarean section and %ost%artum uterine atony and hemorrhage. 9> and 99# Chorioamnionitis accounts for "8A to >8A cases of neonatal se%sis and neonatal res%iratory tract infections. 9;# With %rolonged chorioamnionitis, neonatal morbidity is substantially increased. 9?# Nrether et al. 9<# found that intrauterine e3%osure to maternal infection mar4edly increased the ris4 of cerebral %alsy in term infants. .rom%t efforts to initiate treatment and induce delivery are indicated.

Anesthetic management

$here is no evidence that neura3ial bloc4s are contraindicated in a febrile %arturient with intra*amniotic infection. "# /ecause most obstetricians administer %arenteral antibiotics once the diagnosis of chorioamnionitis has been established, it is =ustified to delay administration of labor analgesia until after the %arturient has received antibiotics. 9@# 1owever, administration of regional anesthesia before antibiotic thera%y in %arturients with intraamniotic infection and %roven bacteremia has not %roven deleterious. ;8 and ;!#

Pneumonia
General considerations
/acterial %neumonia is uncommon in healthy %arturients because of efficient host defense mechanisms. In contrast, alcoholism or drug abuse in %regnancy may im%air consciousness and %redis%ose to inhalation of bacteria*containing secretions leading to %neumonia. /acterial %neumonia is characteriDed by develo%ment of transient chills, followed by a ra%id increase in body core tem%erature. A%%ro3imately ;;A of cases of %neumonia in %regnancy are bacterial in origin. ;"# $he etiology of %neumonia in %regnancy is no different from the non%regnant state. " and ;"# Streptococcus pneumoniae is the most commonly isolated %athogen' however, Haemophilus and Mycoplasma also have been im%licated.

Anesthetic management
$he %hysiologic changes of %regnancy, such as decreased functional residual ca%acity, increased o3ygen consum%tion, ca%illary engorgement, hy%ersecretion of res%iratory tract mucosa, and decreased cellular immunity, may %redis%ose to the develo%ment of %neumonia. A chest radiogra%h should be %erformed to confirm the diagnosis. $he %arturient with %neumonia is susce%tible to the develo%ment of %ulmonary edema. ;"# Su%%lemental o3ygen administration should maintain o3ygen saturation (S%F") above @9A and arterial o3ygen tension (.aF") above ?8 to <8 mm1g. Administration of e%idural anesthesia may attenuate the increased o3ygen consum%tion in laboring %atients with %neumonia. ;0# Ideally, I+ antibiotics should be administered as soon as %ossible before induction of regional anesthesia. When general anesthesia is selected, ra%id desaturation should be antici%ated resulting from increased o3ygen consum%tion characteristic of both %regnancy and infection.

Postpartum infections
$he genital tract is the most common source of %ost%artum infection. 1owever, the %ost%artum infection may also result from %rimary U$I, res%iratory tract infection, and breast infection. <# Clinical manifestations of %ost%artum uterine infection ty%ically include malaise, abdominal %ain, fever, and %urulent lochia. Although ty%ically described as endometritis, %ost%artum uterine infection ty%ically involves decidua, myometrium, and %arametrial tissues. .arturients who underwent abdominal delivery are at increased

ris4 for %ost%artum endometritis when com%ared with %arturients who delivered vaginally. < and 99# .rolonged ru%ture of membranes andCor %rolonged labor increase the incidence of endometritis. $he treatment of endometritis usually includes a%%ro%riate antibiotic thera%y. <#

"eptic shoc#
General considerations
Shoc4 is usually defined as the failure of organ %erfusion, and it may have multi%le causes. Se%tic shoc4 may %otentially com%licate most infectious disorders of %regnancy. &ortunately, this com%lication is infre5uent and usually occurs during the %ost%artum %eriod. Fnce se%tic shoc4 has develo%ed, mortality is very high (00A to ;;A). >; and ;># $he most common etiologies include chorioamnionitis, %yelone%hritis, endometritis, and to3ic shoc4 syndrome. >;# Se%tic shoc4 can be subdivided into early (hy%erdynamic) and late (hy%ovolemic) %hases. $he early %hase of se%tic shoc4 (u% to "> hr) is characteriDed by hy%otension, hy%o%erfusion, low systemic vascular resistance, and increased cardiac out%ut (CF). .rogression to the late %hase is associated with significant fluid losses and decreased CF. .eri%heral vascular resistance is increased and manifested clinically by cold and cyanotic e3tremities. Fliguria and myocardial de%ression are characteristically %resent. Increased concentrations of fibrin degradation %roducts mirror the %resence of disseminated intravascular coagulation (DIC). Adult res%iratory distress syndrome also may develo%. $he diagnosis of se%tic shoc4 is usually established by the develo%ment of %ronounced hy%otension in the %resence of %eri%heral vasodilation. 6a%id and aggressive treatment with I+ fluids, vaso%ressors, and antibiotics is re5uired.

Anesthetic management
Se%tic shoc4 thera%y includes I+ administration of broad*s%ectrum antibiotics and intensive fluid resuscitation, guided by cardiovascular monitoring. If abdominal delivery is indicated, the need for emergent delivery must be often weighed against the need for insertion of invasive monitors and resuscitative efforts aimed at restoring o%timal maternal condition for delivery. $he late %hase of se%tic shoc4 is associated with low CF, intravascular fluid deficits, hy%otension, and coagulo%athy, a combination that usually %recludes the administration of regional anesthesia. ,aternal hemodynamic stability and maintenance of uterine %erfusion should determine the choice of anesthetic drugs for induction and maintenance of general anesthesia. .rolonged induction of anesthesia should be avoided so as to %revent neonatal de%ression at delivery. $he selection of induction drugs should be based on their %redicted cardiovascular res%onse, and drugs that su%%ort the cardiovascular system, such as etomidate or 4etamine, should be selected.

$egional anesthesia for the fe%rile parturient

,any anesthesiologists fear that administration of regional anesthesia in an infected %arturient may s%read the infectious agent to the C7S and lead to neurologic se5uelae of the underlying disease. 1owever, to date, no e%idemiologic study has documented a causal relationshi% between dural %uncture in the %resence of bacteremia and the subse5uent develo%ment of com%lications such as meningitis and e%idural abscess. ;9# 1lavin et al. ;;# re%orted a 8." to !." %er !8,888 incidence of s%ontaneous e%idural abscess in the general hos%ital %o%ulation of %atients. Iindler et al. ;?# re%orted two cases of e%idural abscess in a series of >,!;" %regnant %atients who received labor e%idural analgesia. Another case of an e%idural abscess was described in a %atient who received e%idural anesthesia for cesarean section. ;<# $he develo%ment of Streptococcus*induced bacteremia and meningitis after s%inal anesthesia was re%orted by /lac4more et al. ;@# ,amourian et al. ?8# re%orted three magnetic resonance imaging (,6I) confirmed cases of s%inal*e%idural abscess following combined s%inal*e%idural in=ections. 6ecently, three more cases of meningitis following the increasingly %o%ular combined s%inal*e%idural anesthesia (CS-A) have been described. ?! and ?"# 6eview of the older literature also documents association of s%inal*e%idural abscess and regional anesthesia. ?0# Interestingly, the ma=ority of s%inal*e%idural infections a%%ear to be related to the surgical %rocedure or hematogenous s%read of infectious agent rather than to regional anesthetic techni5ue. ?0# $o date, there are no well*established guidelines for the anesthesiologist in the choice of regional anesthesia for febrile %arturients. Anesthetic management of an infected %atient should be based on an individual ris4*to*benefit ratio, obstetrical indications, and urgency and route of delivery. If general anesthesia is selected for the febrile %regnant %atient, associated ris4 factors such as as%iration of gastric contents, neonatal de%ression, and the %otential for a difficult airway should be antici%ated. ?># $he history and %hysical e3amination, aided by laboratory investigations, will usually identify the etiology of fever. S%inal or e%idural anesthesia, or CS-A, may be safely administered in the %resence of maternal infection and fever. Administration of em%irical antibiotic thera%y is recommended by most authorities and should be initiated as soon as %ossible, before induction of anesthesia. ?9# /ecause o3ygen consum%tion is increased in febrile %atients, su%%lemental o3ygen should be administered to these %arturients with regional anesthesia. $he induction of CS-A, when com%ared with conventional labor e%idural analgesia, has been associated with more ra%id cervical dilation. ?;# /ecause %rolonged labor is a significant ris4 factor for maternal fever, CS-A may be associated with a lower incidence of fever com%ared to conventional e%idural analgesia and thus may become the recommended techni5ue for these %atients.

General anesthesia for the fe%rile patient

Although regional anesthesia is the %referred, and %otentially safer, anesthetic choice for cesarean delivery, as a general rule, general anesthesia remains a viable o%tion for selected %atients with infection and fever. It offers ra%id onset of induction, reliability, and %redictability that are necessary in emergency situations. 1owever, des%ite technical advances in airway management, the conse5uences of failed intubation andCor as%iration

of gastric contents may be catastro%hic. ,aternal mortality rate is !; times higher in %regnant %atients who undergo abdominal delivery with general anesthesia than in those who receive regional anesthesia. ?># Laboring %atients with infection and fever seem more li4ely than nonfebrile %arturients to receive general anesthesia. Uncertainty of fetal tolerance of labor in the %resence of infection, %ossible legal im%lications of delayed delivery, and concerns of a%%ro%riate labor analgesia may create some urgency and lead to abdominal delivery. .reanesthetic evaluation of the infected %arturient should include the cause and duration of fever. U%%er res%iratory tract infections in febrile %arturients may increase oro%haryngeal and bronchial secretions, leading to increased airway irritability. &ever increases maternal o3ygen consum%tion and may com%romise trans%lacental o3ygen delivery to the fetus. .reo3ygenation with !88A o3ygen before induction of general anesthesia is im%ortant in o%timiDing maternal and fetal hemoglobin S%F". ??# As%iration %ro%hyla3is, volume e3%ansion, and correction of electrolyte abnormalities are necessary. In critically ill %atients, the need to %roceed with emergency delivery should be weighed against the need for insertion of invasive monitoring devices such as a central or Swan* NanD catheter, and resuscitation efforts aimed at restoring o%timal maternal condition for delivery. ,aternal hemodynamic stability and maintenance of utero%lacental blood flow should determine the choice of anesthetic drugs for induction and maintenance of general anesthesia in infected %arturients. .rolonged anesthetic induction should be avoided to %revent neonatal de%ression at delivery. ?<# Although ra%id*se5uence induction with cricoid %ressure and I+ administration of thio%ental sodium ?@# or %ro%ofol and succinylcholine is the standard techni5ue, induction drugs that su%%ort the cardiovascular system such as etomidate or 4etamine should be considered. $hio%ental sodium may de%ress myocardial contractility in critically ill %arturients' thus, the use of etomidate is advocated in these %atients. Use of 4etamine also has been recommended, although its hemodynamic effects may be un%redictable in critically ill %atients (including %arturients) with de%leted catecholamine stores. <8# 1y%er4alemia following the use of succinylcholine may be a %roblem in febrile %atients, es%ecially with %rolonged se%sis. <!# $herefore, it is im%ortant to correct fluid and electrolyte abnormalities before induction of anesthesia, and avoid succinylcholine in%atients with hy%er4alemia. 6ocuronium is a suitable alternative to succinylcholine when a nonde%olariDing drug is %referred for ra%id*se5uence induction of general anesthesia for cesarean section. <"# It offers fast onset and intermediate duration of action, and is used for neuromuscular bloc4 in %arturients re5uiring general anesthesia if succinylcholine is contraindicated. <"# $he use of only a single induction drug for intubation when succinylcholine is contraindicated should also be considered. Drug interactions such as those between muscle rela3ants and antibiotics should be antici%ated and a%%ro%riate dose ad=ustment underta4en to %revent %rolonged muscle %aralysis.

&pidural analgesia and maternal intrapartum 'fever(

,aternal fever has been defined as an increase in core body tem%erature above 0<:C in laboring %atient. " and <0# Several investigators recently have investigated the controversy as to whether there is a causal relationshi% between e%idural labor analgesia

and maternal intra%artum Kfever.L <0, <>, <9 and <;# Although it is clear that maternal tem%erature increases in some women who receive labor e%idural analgesia, the cause of the increase remains unresolved. <># $he mechanisms of the association between labor analgesia and maternal fever to date have not been fully elucidated. <0, <>, <; and <?# It has been well established that induction of e%idural anesthesia for surgical %rocedures (including those %rocedures in %regnant %atients) causes sym%athectomy and vasodilation associated with increased heat loss and hy%othermia. 1y%othermia results from redistribution of body heat from the core to the %eri%hery, where the heat is lost to the environment. <<# Fn the contrary, labor e%idural analgesia has been re%orted to cause a gradual increase in maternal core body tem%erature, resulting in hy%erthermia. " and <0# $he mechanism of maternal hy%erthermia following induction of e%idural analgesia remains unclear. .ossible e3%lanations include cessation of hy%erventilation that follows %ain relief, increased incidence of shivering, and decreased sweating. << and <@# Camann et al. @8# studied maternal tem%erature changes in 90 laboring women who received either e%idural analgesia or %arenteral o%ioids for %ain in labor. $ym%anic and oral tem%eratures were monitored in each study grou%. Administration of e%idural analgesia did not affect maternal tem%erature for the first four hours after the induction of analgesia. 1owever, an increase in maternal tem%erature in the e%idural grou% was noted, beginning a%%ro3imately 9 hours after initiation of the bloc4. 7o maternal tem%erature changes were re%orted in %arturients receiving %arenteral o%ioids for labor analgesia. $here was no difference in tem%erature changes between %atients receiving e%idural infusions of local anesthetics alone and e%idural infusions of local anesthetics combined with o%ioids. &usi et al. <@# com%ared %atients receiving e%idural infusion of bu%ivacaine for labor analgesia with those receiving I+ in=ections of me%eridine. ,aternal tem%erature increases averaging 8.!>:CChr were re%orted after induction of e%idural analgesia. 7o increase in maternal tem%erature was noted following I+ me%eridine. It is noteworthy that both investigators (Camann et al. @8# and &usi et al. <@#) administered higher concentrations of bu%ivacaine than those currently em%loyed in obstetric anesthesia %ractice. Interestingly, the tem%erature increases attributed to e%idural analgesia in both studies were subclinical and never e3ceeded 0<:C. &usi et al. suggested that increases in maternal tem%erature resulted from thermoregulatory and vascular modifications caused by labor analgesia. <@# Fther investigators have re%orted similar increases in maternal core tem%erature associated with induction of e%idural analgesia. @! and @"# $he observed tem%erature increase in laboring %atients averaged 8.!8:C %er hour of e%idural analgesia, usually following a lag of > to 9 hours. In contrast to subclinical maternal tem%erature elevation re%orted by &usi et al. <@# and Camman et al. @8# 1erbst et al. @0# analyDed overt maternal fever (0<:C or greater) in "98 women who were matched to "98 other women without fever. ,ore women in the fever grou% received e%idural analgesia (<0A vs. 90A in the control grou%), circumstantially im%licating e%idural analgesia as a cause not only of subclinical tem%erature elevation but also overt, clinical fever. @0# $he authors concluded that, des%ite other ris4 factors such as %rolonged labor and %reterm ru%ture of membranes, there was clearly an inde%endent association between e%idural analgesia and increase in maternal tem%erature. @0#

Nlosten et al. @># evaluated the effect of e%idural analgesia on sweating in non%regnant volunteers. A higher core tem%erature was needed to induce sweating in%atients who received e%idural analgesia. Additionally, decreased sweating was re%orted below the level of sensory bloc4, most li4ely resulting from the bloc4ade of sym%athetic nerve fibers. .anDer et al. @9# showed that many %arturients do not %ers%ire, even in the %resence of fever. Shivering was fre5uently not related to hy%othermia, and sweating was not triggered by hy%othermia in the studied sub=ects. Simultaneous sweating and shivering were re%orted. Iim et al. @;# re%orted that shivering associated with e%idural analgesia was %rimarily caused by normal, %hysiologic, thermoregulatory mechanisms. In contrast, other investigators concluded that shivering was %rimarily caused by a nonthermoregulatory mechanism. @? and @<# A %ossible detrimental effect of maternal fever on the fetus has been a sub=ect of significant controversy. ,acaulay et al. @@# monitored intrauterine and fetal scal% tem%erature in a grou% of 9? %arturients. Increased intrauterine tem%erature was noted in%atients who received labor e%idural analgesia. $hree of 9? fetuses had scal% tem%erature e3ceeding 0@:C. @@# Camann et al. @8# concluded that e%idural analgesia is unli4ely to increase maternal tem%erature sufficiently enough to have an adverse effect on the fetus. Lieberman et al. @!# re%orted an association between e%idural analgesia, maternal fever, and neonatal se%sis evaluation. $he study, which originally intended to evaluate active management of labor, re%orted a fre5uency of fever ranging from ?A to 0;A in %arturients receiving e%idural analgesia. &ever was re%orted in ?A of %arturients receiving e%idural analgesia with labor duration less than ; hours, and increased to 0;A of %arturients who were in labor for more than !< hours. $he fre5uency of fever in laboring %atients who did not receive e%idural analgesia remained a%%ro3imately !A, regardless of the duration of labor. 7eonatal se%sis evaluation was %erformed in 0>A of neonates born to febrile mothers in the e%idural grou%, com%ared with @.<A in the none%idural grou%. Interestingly, the fre5uency of confirmed neonatal se%sis did not differ between the two study grou%s, and was re%orted in less than !A of neonates. Unfortunately, the study was not randomiDed, and the two grou%s of %atients differed significantly. In addition, the s%ecific criteria for neonatal se%sis evaluations were not %recisely established, and more than ;0A of neonatal se%sis evaluations were %erformed for reasons other than maternal fever. 7evertheless, logistic regression analysis confirms the association between e%idural analgesia and fever even after consideration of other variables. !88# .hili% et al. !88# %ros%ectively randomiDed ;!0 laboring women to either an e%idural or I+ me%eridine analgesia study grou%. When com%ared with I+ me%eridine administration, the e%idural labor analgesia was inde%endently associated with maternal tem%erature increase. $he fre5uency of neonatal se%sis evaluations was strongly associated with the %resence of maternal fever. In conclusion, there seems to be enough evidence to su%%ort an association between e%idural labor analgesia and maternal tem%erature elevation, es%ecially after four or more hours since the induction of anesthesia. <@, @8, @!, @0, @@ and !88# 1owever, most of the studies were not randomiDed, and for that reason %atient selection bias cannot be eliminated. In contrast, there is no evidence that fre5uency of confirmed neonatal se%sis is increased in neonates born to mothers who received e%idural analgesia for labor. $he

association between labor e%idural analgesia and neonatal se%sis evaluation (wor4u%) is less clear. ,any factors other than maternal fever are involved in the decision*ma4ing %rocess leading to initiation of a neonatal se%sis evaluation. &inally, most randomiDed studies com%ared tem%erature changes in%atients who received e%idural analgesia with control grou%s who received %arenteral me%eridine. !88# ,e%eridine is 4nown to selectively decrease the shivering threshold, and it is used widely as a treatment of %osto%erative shivering. $herefore, its selection as a control grou% remains 5uestionable, and further investigations are needed.

"ummary
$he administration of e%idural anesthesia in healthy %arturients in labor has been associated with a modest increase in maternal core tem%erature. 1owever, there is lac4 of evidence to suggest that this transient increase in maternal tem%erature adversely affects the fetus. $here are many anesthetic challenges in the management of the infected %regnant %atient (both in elective manner and emergency situations). A com%lete understanding of %hysiology of %regnancy, combined with the 4nowledge of etiology and %atho%hysiology of the coe3isting disease %rocess is therefore essential in contem%orary anesthesia %ractice. $he anesthesiologist may safely administer regional anesthesia to the ma=ority of %atients with established infection, %rovided that se%sis is not %resent. 1owever, it seems %rudent to determine the etiology of infection and initiate a%%ro%riate thera%y with antibiotics before induction of anesthesia.

Ac#nowledgement
$he author would li4e to than4 Dr. IrDysDtof ,. IucD4ows4i for his 4ind %ermission to use this article for the summary of the Anesthetic ,anagement of the .arturient with &ever and Infection.

$eferences
!. 6.I. Stoelting and S.&. Dierdorf, Infectious diseases. InO 6.I. Stoelting and S.&. Dierdorf, -ditors, Anesthesia and Co !"isting #isease, 3rd ed, Churchill Livingstone, 7ew Por4 (!@@0), %%. >9@Q><0. ". S.1. 6olbin and /.A. ,orningstar, $he febrile %arturient. InO D.R. /irnbach, S... Natt and S. Datta, -ditors, Te"tboo$ o% &bstetric Anesthesia, Churchill Livingstone, 7ew Por4 ("888), %%. 0?9Q0@!. 0. L.I. Worthley and 7. ,atthews, Disorders of body tem%erature. InO L.I. Worthley and 7. ,atthews, -ditors, Synopsis o% 'ntensive Care Medicine, Churchill Livingstone, London (!@@>), %%. ?"!Q?08. >. ,.R. Iluger, W. IoDa4, L.6. Leon, D. SosDyns4i and C.A. Conn, &ever and anti%yresis. (rog )rain *es ))* (!@@<), %%. >;9Q>?9. 9. ,.R. Iluger, W. IoDa4, C.A. Conn, L.6. Leon and D. SosDyns4i, 6ole of fever in disease. Ann +, Acad Sci +, (!@@<), %%. "">Q "00. ;. -. At4ins, &ever Q new %ers%ectives on an old %henomenon. + !ngl - Med -./ (!@<0), %%. @9<Q@;@. ?. 6.N. ,c,urray, +.L. IatD, ,.R. /erry and 6.C. Cafalo, $he effect of %regnancy on metabolic res%onses during rest, immersion, and aerobic e3ercise in the water. Am - &bstet .ynecol )*/ (!@<<), %%. ><!Q><;. <. 6.C. Noodlin and R.W. Cha%in, Determinants of maternal tem%erature during labor. Am - &bstet .ynecol )0- (!@<"), %%. @?Q!80. @. 6.S. Nibbs and 6.L. Sweet, ,aternal and fetal infections. InO 6.I. Creasy and 6. 6esni4, -ditors, Maternal /etal Medicine0 (rinciples and (ractice, W. /. Saunders, .hiladel%hia (!@@8), %%. ;9;Q?"9. !8. 1. Car% and S. /ailey, $he association between meningitis and dural %uncture in bacteremic rats. Anesthesiology 12 (!@@"), %%. ?0@Q?>". !!. 7./. Isada and R.1. Nrossman, .erinatal infections. InO S.N. Nabbe, R.6. 7iebyl and R.L. Sim%son, -ditors, &bstetrics +ormal and (roblem (regnancies, Churchill Livingstone, 7ew Por4 (!@@!), %%. !"><Q!";!. !". L.,. 1ollier, L.L. Scott, S.S. ,ur%hree and N.D. Wendel, Rr, .ost%artum endometritis caused by her%es sim%le3 virus. &bstet .ynecol /, (!@@?), %%. <0;Q<0<.

!0. ..A. 1ensleigh, W.W. Andrews, S. /rown, R. Nreens%oon, L. Pasu4awa and C.N. .rober, Nenital her%es during %regnancyO inability to distinguish %rimary and recurrent infections clinically. &bstet .ynecol /, (!@@?), %%. <@!Q<@9. !>. L.L. Scott, L.,. 1ollier and I. Dias, .erinatal her%esvirus infections. 1er%es sim%le3, varicella, and C,+. 'n%ect #is Clin +orth Am )) (!@@?), %%. "?Q90. !9. S.A. /rown, L.A. +ontver, R. /enedetti et al., -ffects on infants of a first e%isode of genital her%es during %regnancy. + !ngl Med -)1 (!@<?), %%. !">;Q!"9!. !;. A.,. /ader, W.6. Camann and S. Datta, Anesthesia for cesarean delivery in %atients with her%es sim%le3 virus ty%e*" infections. *eg Anesth )* (!@@8), %%. ";!Q";0. !?. S. 6amanathan, 6. Sheth and 1. $urndorf, Anesthesia for cesarean section in %atients with genital her%es infectionsO a retros%ective study. Anesthesiology 20 (!@<;), %%. <8?Q<8@. !<. -.$. Crosby, S.1. 1al%ern and S.1. 6olbin, -%idural anaesthesia for caesarean section in %atients with active recurrent genital her%es sim%le3 infectionsO a retros%ective review. Can - Anaesth -2 (!@<@), %%. ?8!Q?8>. !@. ,.A. +alley, D.L. /our4e and A.,. ,cIenDie, 6ecurrence of thoracic and labial her%es sim%le3 virus infection in a %atient receiving e%idural fentanyl. Anesthesiology 12 (!@@"), %%. !89;Q!89?. "8. C.&. Rames, 6ecurrence of her%es sim%le3 virus ble%haritis after cesarean section and e%idural mor%hine. Anesth Analg /+ (!@@;), %%. !8@>Q!8@;. "!. 6.I. /oyle, A review of anatomical and immunological lin4s between e%idural mor%hine and her%es sim%le3 labialis in obstetric %atients. Anaesth 'ntensive Care +- (!@@9), %%. >"9Q>0". "". 6.I. /oyle, 1er%es sim%le3 labialis after e%idural or %arenteral mor%hineO a randomiDed %ros%ective trial in an Australian obstetric %o%ulation. Anaesth 'ntensive Care +- (!@@9), %%. >00Q>0?. "0. ,.C. 7orris, R. Weiss and /.L. Leighton, $he incidence of her%es sim%le3 virus labialis after cesarean delivery. 'nt - &bstet Anesth - (!@@>), %%. !"?Q!0!. ">. ,.C. Sambon and D.,. Loc4wood, 1e%atitis C seroconversion in %regnancy. )r - &bstet .ynaecol ).) (!@@>), %%. ?""Q?">. "9. N.D. Ielen, N./. Nreen, 6.1. .urcell et al., 1e%atitis / and he%atitis C in emergency de%artment %atients. + !ngl - Med -+2 (!@@"), %%. !0@@Q!>8>. ";. I.,. IucD4ows4i, D.R. /irnbach and A. van Sundert, Drug abuse in the %arturient. Semin Anesth (eriop Med (ain ), ("888), %%. "!;Q"">. "?. 6. We=stal, A. Widell, A.S. ,ansson, S. 1ermodsson and N. 7or4rans, ,other*to*infant transmission of he%atitis C virus. Ann 'ntern Med ))1 (!@@"), %%. <<?Q<@8. "<. W1F Neneva, Wee4ly -%idemiological 6ecord. !@@?'"?O!@?*"88 "@. ,.D. 7ewman and C./. Wofsy, Nender*s%ecific issues in 1I+ disease. InO ,.A. Sande and ..A. +olberding, -ditors, The Medical Management o% A'#S (9th ed.),, W. /. Saunders, .hiladel%hia (!@@?), %%. >?9Q>@8. 08. S.C. 1ughes, AIDSO the focus turns to women. 'nt - &bstet Anesthesiol + (!@@0), %%. !Q". 0!. N. Fgilvie, S. Adsett and N. ,acdonald, Do %hysicians discuss 1I+ testing during %renatal careT. Can /am (hysician 0- (!@@?), %%. !0?;Q!0<!. 0". A.S. &auci and 1.C. Lane, 1uman immunodeficiency virus (1I+) diseaseO AIDS and related disorders. InO I.R. Isselbacher et al.Harrison1s (rinciples o% 'nternal Medicine, ,cNraw*1ill, 7ew Por4 (!@@>), %%. !<9"Q!@!0. 00. D.,. $hea, 6.W. Ste4etee, +. .liner et al., $he effect of maternal viral load on the ris4 of %erinatal transmission of 1I+*!. 7ew Por4 City .erinatal 1I+ $ransmission Collaborative Study Nrou%. A'#S )) (!@@?), %%. >0?Q>>>. 0>. .. Stratton, 6.-. $uomala, 6. Abboud et al., Fbstetric and newborn outcomes in a cohort of 1I+ infected %regnant womenO a re%ort of the women and infants transmission study. - Ac2uir 'mmune #e%ic Syndr Hum *etrovirol +. (!@@@), %%. !?@Q!<;. 09. ..A. ,oc4, 7. Shaffer, C. /hadra4om et al., ,aternal viral load and timing of mother*to*child 1I+ transmission, /ang4o4, $hailand. /ang4o4 Collaborative .erinatal 1I+ $ransmission Study Nrou%. A'#S )- (!@@@), %%. >8?Q>!>. 0;. ,.-. St. Louis, ,. Iamenga, C. /rown et al., 6is4 for %erinatal 1I+*! transmission according to maternal immunologic, virologic, and %lacental factors. -AMA +2, (!@@0), %%. "<90Q"<9@. 0?. C. Iind, C. 6udin, C.A. Siegrist et al., .revention of vertical 1I+ transmissionO additive %rotective effect of elective Cesarean section and Didovudine %ro%hyla3is. Swiss 7eonatal 1I+ Study Nrou%. A'#S )+ (!@@<), %%. "89Q"!8. 0<. I.,. IucD4ows4i and D.R. /irnbach, $he 1I+*infected %arturientO is neura3ial anesthesia contraindicatedT. Curr Anesthesiol *ep + ("888), %%. !!<Q!"!. 0@. -.6. Nreene, Rr, S%inal and e%idural anesthesia in %atients with the ac5uired immunodeficiency syndrome. Anesth Analg 2* (!@<;), %%. !8@8Q!8@!. >8. S.C. 1ughes, ..A. Dailey, D. Landers, /.R. Dattel, W.6. Crombleholme and R.L. Rohnson, .arturients infected with human immunodeficiency virus and regional anesthesia. Clinical and immunologic res%onse. Anesthesiology /+ (!@@9), %%. 0"Q0;. >!. ,.D. IanDer, 7euro%athology of AIDS. Crit *ev +eurobiol * (!@@8), %%. 0!0Q0;". >". D.R. $om, S.R. Nulevich, 1.,. Sha%iro, 6.I. 1eaton and I. Nrant, -%idural blood %atch in the 1I+*%ositive %atient. 6eview of clinical e3%erience. San Diego 1I+ 7eurobehavioral 6esearch Center. Anesthesiology 12 (!@@"), %%. @>0Q@>?. >0. S.7. ,ar4ovic, ..6. Inight and D.,. ,aras4o, Inhibition of interferon stimulation of natural 4iller cell activity in mice anesthetiDed with halothane or isoflurane. Anesthesiology 1/ (!@@0), %%. ?88Q?8;. >>. ,.S. Iristensen, -. Sloth and $.I. Rensen, 6elationshi% between anesthetic %rocedure and contact of anesthesia %ersonnel with %atient body fluids. Anesthesiology 1- (!@@8), %%. ;!@Q;">. >9. R.L. Nerberding, Limiting the ris4s of health care wor4ers. InO ,.A. Sande and ..A. +olberding, -ditors, The Medical Management o% A'#S (9th ed ed.),, W. /. Saunders, .hiladel%hia (!@@?), %%. 9>Q;>. >;. W. Lee, S.L. Clar4, D./. Cotton et al., Se%tic shoc4 during %regnancy. Am - &bstet .ynecol )*, (!@<<), %%. >!8Q>!;. >?. D.,. $wic4ler, ,.R. Lucas, L. /owe, D.D. ,cIntire, R. /arron and &.N. Cunningham, Ultrasonogra%hic evaluation of central and end*organ hemodynamics in ante%artum %yelone%hritis. Am - &bstet .ynecol )1. (!@@>), %%. <!>Q<!<. ><. ,.R. Lucas and &.N. Cunningham, Urinary infection in %regnancy. Clin &bstet .ynecol -2 (!@@0), %%. <99Q<;<. >@. &.N. Cunningham, ,.R. Lucas and N.D. 1an4ins, .ulmonary in=ury com%licating ante%artum %yelone%hritis. Am - &bstet .ynecol )*2 (!@<?), %%. ?@?Q<8". 98. R.,. Ale3ander, D.,. ,cIntire and I.R. Leveno, Chorioamnionitis and the %rognosis for term infants. &bstet .ynecol ,0 (!@@@), %%. "?>Q"?<.

9!. D.A. -schenbach, Amniotic fluid infection and cerebral %alsy. &ocus on the fetus. -AMA +1/ (!@@?), %%. ">?Q"><. 9". 6.S. Nibbs and .. Duff, .rogress in %athogenesis and management of clinical intraamniotic infection. Am - &bstet .ynecol )20 (!@@!), %%. !0!?Q!0";. 90. /.,. Casey and S.,. Co3, Chorioamnionitis and endometritis. 'n%ect #is Clin +orth Am )) (!@@?), %%. "80Q""". 9>. .. Duff, 6. Sanders and 6.S. Nibbs, $he course of labor in term %atients with chorioamnionitis. Am - &bstet .ynecol )01 (!@<0), %%. 0@!Q0@9. 99. ..6. Poder, 6.S. Nibbs, R.D. /lanco, P.S. Castaneda and ..R. St Clair, A %ros%ective, controlled study of maternal and %erinatal outcome after intra*amniotic infection at term. Am - &bstet .ynecol )0* (!@<0), %%. ;@9Q?8!. 9;. -.6. 7ewton, Chorioamnionitis and intraamniotic infection. Clin &bstet .ynecol -2 (!@@0), %%. ?@9Q<8<. 9?. D.R. ,ur%hy, S. Sellers, I.S. ,acIenDie, ..L. Pudin and A.,. Rohnson, Case*control study of antenatal and intra%artum ris4 factors for cerebral %alsy in very %reterm singleton babies. 3ancet -02 <@<< (!@@9), %%. !>>@Q!>9>. 9<. R.I. Nrether and I./. 7elson, ,aternal infection and cerebral %alsy in infants of normal birth weight. -AMA +1/ (!@@?), %%. "8?Q "!! 9@. P. /eilin, C.A. /odian, -.,. 1addad and A./. LeibowitD, .ractice %atterns of anesthesiologists regarding situations in obstetric anesthesia where clinical management is controversial. Anesth Analg /- (!@@;), %%. ?09Q?>!. ;8. -.R. Noodman, -. De1orta and R.,. $aguiam, Safety of s%inal and e%idural anesthesia in %arturients with chorioamnionitis. *eg Anesth +) (!@@;), %%. >0;Q>>!. ;!. A.,. /ader, L. Nilbertson, L. IirD and S. Datta, 6egional anesthesia in women with chorioamnionitis. *eg Anesth )1 (!@@"), %%. <>Q<;. ;". L.A. Noodrum, .neumonia in %regnancy. Sem (erinatol +) (!@@?), %%. "?;Q"<0. ;0. W.-. Ac4erman, III, R.,. ,olnar and ,.,. Rune=a, /eneficial effect of e%idural anesthesia on o3ygen consum%tion in a %arturient with res%iratory distress syndrome. South Med - /2 (!@@0), %%. 0;!Q0;>. ;>. W.C. ,abie, R.6. /arton and /. Sibai, Se%tic shoc4 in %regnancy. &bstet .ynecol ,. (!@@?), %%. 990Q9;!. ;9. S. Segal, 1. Car% and D.1. Chestnut, &ever and infection. InO D.1. Chestnut, -ditor, &bstetric Anesthesia (rinciples and (ractice, ,osby, St. Louis (!@@@), %%. ?!!Q?">. ;;. ,.L. 1lavin, 1.R. Iamins4i, R.S. 6oss and -. NanD, S%inal e%idural abscessO a ten*year %ers%ective. +eurosurgery +1 (!@@8), %%. !??Q!<>. ;?. C. Iindler, ,. Seeberger, ,. Siegemund and ,. Schneider, -3tradural abscess com%licating lumbar e3tradural anaesthesia and analgesia in an obstetric %atient. Acta Anaesthesiol Scand 0. (!@@;), %%. <9<Q<;!. ;<. W.D. Iee, ,.6. Rones, .. $homas and 6.R. Worth, -3tradural abscess com%licating e3tradural anaesthesia for caesarean section. )r - Anaesth 2, (!@@"), %%. ;>?Q;9". ;@. $.I. /lac4more, 1.6. ,orley and D.L. Nordon, Stre%tococcus mitis*induced bacteremia and meningitis after s%inal anesthesia. Anesthesiology 1/ (!@@0), %%. 9@"Q9@>. ?8. A.C. ,amourian, C.A. Dic4man, /... Drayer and +.I. Sonntag, S%inal e%idural abscessO three cases following s%inal e%idural in=ection demonstrated with magnetic resonance imaging. Anesthesiology 1/ (!@@0), %%. "8>Q"8?. ?!. ,. Cascio and N. 1eath, ,eningitis following a combined s%inal*e%idural techni5ue in a labouring term %arturient. Can - Anaesth 0- (!@@;), %%. 0@@Q>8". ?". S.A. 1arding, 6.-. Collins and /.,. ,organ, ,eningitis after combined s%inal*e3tradural anaesthesia in obstetrics. )r - Anaesth 1- (!@@>), %%. 9>9Q9>?. ?0. A.S. /a4er, 6.N. F=emann, ,.7. SwartD and -... 6ichardson, Rr, S%inal*e%idural abscess. + !ngl - Med +,- (!@?9), %%. >;0Q>;<. ?>. R.L. 1aw4ins, L.,. Ioonin, S.I. .almer and C... Nibbs, Anesthesia*related deaths during obstetric delivery in the United States, !@?@*!@@8. Anesthesiology /2 (!@@?), %%. "??Q"<>. ?9. D.1. Chestnut, S%inal anesthesia in the febrile %atient. Anesthesiology 12 (!@@"), %%. ;;?Q;;@. ?;. L. $sen, /. $hue, S. Datta and S. Segal, Is combined s%inal*e%idural analgesia associated with more ra%id cervical dilation in nulli%arous %atients when com%ared with conventional e%idural analgesiaT. Anesthesiology ,) (!@@@), %%. @"8Q@"9. ??. &. /yrne, A. Fduro*Dominah and 6. Ii%ling, $he effect of %regnancy on %ulmonary nitrogen washout. A short study of %re* o3ygenation. Anaesthesia 0+ (!@<?), %%. !><Q!98. ?<. S. Datta, N.W. Fstheimer, R./. Weiss, W.U. /rown, Rr. and ,.1. Al%er, 7eonatal effect of %rolonged anesthetic induction for cesarean section. &bstet .ynecol */ (!@<!), %%. 00!Q009. ?@. A.,. ,alinow, Neneral anesthesia for cesarean delivery. InO ,.C. 7orris, -ditor, &bstetric Anesthesia, Li%%incott Williams U Wil4ins, .hiladel%hia (!@@@), %%. 0?9Q0@0. <8. /. Iohlschutter, 1. /aur and &. 6oth, Su3amethonium*induced hy%er4alaemia in %atients with severe intra*abdominal infections. )r - Anaesth 0/ (!@?;), %%. 99?Q9;". <!. W.L. Way and A.R. $revor, Ietamine. InO 6.D. ,iller, -ditor, Anesthesia, Churchill Livingstone, 7ew Por4 (!@<;), %%. <!0Q<!>. <". L.S. 6eisner and D. Lin, Anesthesia for cesarean section. InO D.1. Chestnut, -ditor, &bstetric Anesthesia (rinciples and (ractice, ,osby, St. Louis (!@@@), %%. >;9Q>@". <0. C.,. +iscomi and $. ,anullang, ,aternal fever, neonatal se%sis evaluation, and e%idural labor analgesia. *eg Anesth (ain Med +* ("888), %%. 9>@Q990. <>. R.S. Dashe, /./. 6ogers, D.D. ,cIntire and I.R. Leveno, -%idural analgesia and intra%artum feverO %lacental findings. &bstet .ynecol ,- (!@@@), %%. 0>!Q0>>. <9. /. Iaul, ,. +alle=o, S. 6amanathan and N. ,andell, -%idural labor analgesia and neonatal se%sis evaluation rateO a 5uality im%rovement study. Anesth Analg ,- ("88!), %%. @<;Q@@8. <;. A. .etrova, I. Demissie, N.N. 6hoads, R.C. Smulian, S. ,arcella and C.+. Ananth, Association of maternal fever during labor with neonatal and infant morbidity and mortality. &bstet .ynecol ,/ ("88!), %%. "8Q"? <?. L.S. .olley, WhatJs new in obstetric anesthesia, !@@@T. 'nt - &bstet Anesthesiol ). ("88!), %%. >;Q9>. <<. R.,. 1ynson, D.I. Sessler, /. Nlosten and R. ,cNuire, $hermal balance and tremor %atterns during e%idural anesthesia. Anesthesiology 10 (!@@!), %%. ;<8Q;@8. <@. L. &usi, ..R. Steer, ,.R. ,aresh and 6.W. /eard, ,aternal %yre3ia associated with the use of e%idural analgesia in labor. 3ancet ) <;>@ (!@<@), %%. !"98Q!"9".

@8. W.6. Camann, L.A. 1ortvet, 7. 1ughes, A.,. /ader and S. Datta, ,aternal tem%erature regulation during e3tradural analgesia for labour. )r - Anaesth 21 (!@@!), %%. 9;9Q9;<. @!. -. Lieberman, R.,. Lang, &. &rigoletto, Rr, D.I. 6ichardson, S.A. 6inger and A. Cohen, -%idural analgesia, intra%artum fever, and neonatal se%sis evaluation. (ediatrics ,, (!@@?), %%. >!9Q>!@. @". D.C. ,ayer, 7.C. Cherscheir and &.R. S%ielman, Increased intra%artum antibiotic administration associated with e%idural analgesia in labor. Am - (erinatol )0 (!@@?), %%. <0Q<;. @0. A. 1erbst, .. Wolner*1anssen and I. Ingemarsson, ,aternal fever in term labour in relation to fetal tachycardia, cord artery acidaemia and neonatal infection. )r - &bstet .ynaecol ).0 (!@@?), %%. 0;0Q0;;. @>. /. Nlosten, ,. Savage, N.A. 6oo4e and N.L. /rengelmann, -%idural anesthesia and the thermoregulatory res%onses to hy%erthermiaG%reliminary observations in volunteer sub=ects. Acta Anaesthesiol Scand 0+ (!@@<), %%. >>"Q>>;. @9. F. .anDer, 7. NhaDanfari, D.I. Sessler et al., Shivering and shivering*li4e tremor during labor with and without e%idural analgesia. Anesthesiology ,. (!@@@), %%. !;8@Q!;!;. @;. R.S. Iim, $. I4eda, D.I. Sessler, ,. $ura4hia and 6. Reffrey, -%idural anesthesia reduces the gain and ma3imum intensity of shivering. Anesthesiology // (!@@<), %%. <9!Q<9?. @?. D. /uggy and R. Nardiner, $he s%ace blan4et and shivering during e3tradural analgesia in labour. Acta Anaesthesiol Scand -, (!@@9), %%. 99!Q990. @<. R. .onte, /.R. Collett and A. Walmsley, Anaesthetic tem%erature and shivering in e%idural anaesthesia. Acta Anaesthesiol Scand -. (!@<;), %%. 9<>Q9<?. @@. R.1. ,acaulay, I. /ond and ..R. Steer, -%idural analgesia in labor and fetal hy%erthermia. &bstet .ynecol /. (!@@"), %%. ;;9Q ;;@. !88. R. .hili%, R.,. Ale3ander, S.I. Sharma, I.R. Leveno, D.D. ,cIntire and R. Wiley, -%idural analgesia during labor and maternal fever. Anesthesiology ,. (!@@@), %%. !"?!Q!"?9.