FeverNCT00326521
Evaluation of Fever Occurring in Labor in Patients Receiving Epidural Anesthesia
An observational study of Fever, run by MemorialCare at 2 sites in United States.
Trial summary
Briefly, the investigators propose to evaluate nulliparous (first time mothers) patients beyond 36 0/7 weeks' gestation in active labor who already have received epidural anesthesia and have an intrauterine pressure catheter (IUPC) in place. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Fever
- How many people
- 50 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2006to May 2009
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Women >18 years of age that present to labor and delivery and are in active labor.
Who may be able to join
- Nulliparous
- Maternal age > 18 years of age
- Estimated gestational age (EGA) > 36 0/7 weeks
- Active labor (> 4 cm dilated)
- Epidural anesthesia
- IUPC in place prior to development of fever
- Temperature of > 38 degrees
- Consents to study
Who cannot join
- Multiparous
- Maternal age < 18 years of age
- External tocometer
Trial locations and contacts
2 sites in 1 country.
United States2 sites, 2 recruiting
- Recruiting
Long Beach Memorial Medical Center
Long Beach, California, 90806
Christine Preslicka, RN, 562-933-2755, cpreslicka@memorialcare.org
Michael P Nageotte, MD, 562-933-2730, mnageotte@memorialcare.org
- Recruiting
UCI Medical Center
Orange, California, 92686
Pam Rumney, RN, 714-456-5967, prumney@uci.edu
Deborah Wing, MD, 714-456-5967, dwing@uci.edu
About this study
Official title: Evaluation of Intrapartum Fever in Patients Receiving Epidural Anesthesia
Briefly, the investigators propose to evaluate nulliparous (first time mothers) patients beyond 36 0/7 weeks' gestation in active labor who already have received epidural anesthesia and have an intrauterine pressure catheter (IUPC) in place. Any patient who then develops a single temperature elevation of > 38 degrees will be eligible for inclusion and consented for the study. Maternal blood will be drawn immediately, one hour later and at delivery. Amniotic fluid will be aspirated from the pressure catheter; the first 1-2 cc will be discarded and the remainder will be evaluated for gram stain, culture, glucose level, interleukin-6 (IL-6), and proteomics. All placentas will be sent for routine pathologic examination. Cord blood will be obtained at birth for routine studies. Both maternal and cord blood will be sent for proteomic evaluation (defined). The patients with amniotic fluid that has a positive gram stain and culture will be defined as the infected group, and the patients with amniotic fluid that has a negative gram stain and culture will be defined as the uninfected group. Differences in clinical presentation and laboratory assessments, including proteomics, will be compared between the two groups to determine if there are any markers that might prove to be useful in distinguishing between these two entities (epidural fever with and without actual infection).
Read the detailed description
Historically the diagnosis of chorioamnionitis (an infection of the membranes surrounding the fetus) for patients in labor has been made on the basis of multiple clinical variables such as maternal fever, fetal tachycardia, uterine tenderness, or foul smelling vaginal discharge. The diagnosis also takes into account a clinical picture consistent with risk factors such as prolonged labor and prolonged rupture of membranes. Since most of these findings are not specific, chorioamnionitis becomes the diagnosis of exclusion unless there is another explanation for the fever. Randomized studies have clearly shown that maternal antibiotics and neonatal septic work-ups are indicated once the diagnosis of chorioamnionitis has been made. Neonatal sepsis is a severe infection of the blood stream. Such policies have important implications for health care providers, on the impact of medical costs, and on the duration of hospital stay. This becomes especially true for the newborn that is transferred to the neonatal intensive care unit (NICU) for sepsis evaluation. Often times, these newborns are prophylactically treated with antibiotics based on the suspicion of an infection, while waiting for finalized blood culture results. Since newborn sepsis is such a difficult diagnosis to make, many more newborns are treated than actually have the disease and the length of their hospital stay may be significantly increased.
Over the past 15 years, both observational and randomized trials have observed an increase in maternal fever associated with epidural anesthesia in labor. These trials have shown increased ranges from 10 - 15% over baseline rates and an increased relative risk of 1.5 to 15 fold, and even up to 70 fold in one study, over the rates seen in women not receiving epidural anesthesia. After correcting for duration of labor and other confounding variables, these increases remained present. Since epidural fever is virtually impossible to distinguish from chorioamnionitis-related fever, these women are almost all treated with antibiotics and given the diagnosis of infection. This approach also has tremendous impact on the evaluation and care of the newborn. Two specific studies evaluated this impact on the neonate. Lieberman found that babies of mothers given epidural anesthesia were more likely to be evaluated for sepsis (34 vs. 9%) and treated with antibiotics (15 vs. 4%). Similarly, Philips found the same increase (25 vs. 16% and 19 vs. 11%). Both studies had very low rates of confirmed neonatal sepsis. On a national basis, the cost of this confusion nationally is tremendous.
There is one known way to distinguish between true chorioamnionitis in labor and non-infectious fever due to the epidural anesthesia. Gibbs and colleagues found that amniotic fluid aspirated from an intrauterine pressure catheter, a device commonly utilized for monitoring contractions in labor, could be used to accurately make the diagnosis of infection using gram stain and culture. More recently, many papers have shown that low glucose levels and elevated IL-6 in amniotic fluid were also accurate tests for infection. While these markers could in theory be used for distinguishing between epidural fever and true chorioamnionitis, most patients do not require such a device and this approach would not likely gain widespread favor. Alternatively, however, this approach could be used as a research tool in women who already have such a catheter in place to determine if there are additional non-invasive clinical or laboratory markers to distinguish one from the other.
Recently proteomic assessment has become an extremely effective tool in determining if there are certain markers for various diseases. Proteomics is the determination of the structure, function, and expression of all of the corresponding proteins that are encoded within the genome structure. It can also be defined as the "fingerprint" of a disease process. It involves running tandem mass spectometry on the fluid of interest. Such an approach could be extremely valuable both in determining whether the mother actually has chorioamnionitis and, if so, whether there are better markers for neonatal sepsis.
- Conditions
- Fever
- Keywords
- Pregnant Women, Epidural Anesthesia, Fever, Chorioamnionitis, Intrauterine pressure catheter, Pregnancy
- Medical subject headings
- Fever, Chorioamnionitis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2006 (estimated)
- Study startOct 2006
- Study completionMay 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for FeverStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- MemorialCare
- Sponsor type
- University, hospital or other
- Investigators
- Michael P Nageotte, MD, Principal investigator, Memorial Care
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00326521
- Sponsor's protocol ID
- 297-05
- Status last verified
- Jun 2008
- First submitted
- 15 May 2006
- Last updated
- 6 Jun 2008
- Results posted
- No
- Data monitoring committee
- No
Publications
Gibbs RS, Blanco JD, St Clair PJ, Castaneda YS. Quantitative bacteriology of amniotic fluid from women with clinical intraamniotic infection at term. J Infect Dis. 1982 Jan;145(1):1-8. doi: 10.1093/infdis/145.1.1.
PubMed 7033397Lieberman E, O'donoghue C. Unintended effects of epidural analgesia during labor: a systematic review. Am J Obstet Gynecol. 2002 May;186(5 Suppl Nature):S31-68. doi: 10.1067/mob.2002.122522.
PubMed 12011872Ramin SM, Gambling DR, Lucas MJ, Sharma SK, Sidawi JE, Leveno KJ. Randomized trial of epidural versus intravenous analgesia during labor. Obstet Gynecol. 1995 Nov;86(5):783-9. doi: 10.1016/0029-7844(95)00269-w.
PubMed 7566849Yancey MK, Zhang J, Schwarz J, Dietrich CS 3rd, Klebanoff M. Labor epidural analgesia and intrapartum maternal hyperthermia. Obstet Gynecol. 2001 Nov;98(5 Pt 1):763-70. doi: 10.1016/s0029-7844(01)01537-x.
PubMed 11704166Lieberman E, Lang JM, Frigoletto F Jr, Richardson DK, Ringer SA, Cohen A. Epidural analgesia, intrapartum fever, and neonatal sepsis evaluation. Pediatrics. 1997 Mar;99(3):415-9. doi: 10.1542/peds.99.3.415.
PubMed 9041298Chen KT, Ringer S, Cohen AP, Lieberman E. The role of intrapartum fever in identifying asymptomatic term neonates with early-onset neonatal sepsis. J Perinatol. 2002 Dec;22(8):653-7. doi: 10.1038/sj.jp.7210818.
PubMed 12478449
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Intrapartum Fever in Patients Receiving Epidural Anesthesia
- ClinicalTrials.gov ID
- NCT00326521
- Acronym / sponsor ID
- 297-05
- Conditions
- Fever
- Keywords
- Pregnant Women, Epidural Anesthesia, Fever, Chorioamnionitis, Intrauterine pressure catheter, Pregnancy
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- MemorialCareUniversity, hospital or other
- Study start
- Oct 2006
- Study completion
- May 2009 (estimated)
- First posted
- 17 May 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Briefly, the investigators propose to evaluate nulliparous (first time mothers) patients beyond 36 0/7 weeks' gestation in active labor who already have received epidural anesthesia and have an intrauterine pressure catheter (IUPC) in place. Any patient who then develops a single temperature elevation of > 38 degrees will be eligible for inclusion and consented for the study. Maternal blood will be drawn immediately, one hour later and at delivery. Amniotic fluid will be aspirated from the pressure catheter; the first 1-2 cc will be discarded and the remainder will be evaluated for gram stain, culture, glucose level, interleukin-6 (IL-6), and proteomics. All placentas will be sent for routine pathologic examination. Cord blood will be obtained at birth for routine studies. Both maternal and cord blood will be sent for proteomic evaluation (defined). The patients with amniotic fluid that has a positive gram stain and culture will be defined as the infected group, and the patients with amniotic fluid that has a negative gram stain and culture will be defined as the uninfected group. Differences in clinical presentation and laboratory assessments, including proteomics, will be compared between the two groups to determine if there are any markers that might prove to be useful in distinguishing between these two entities (epidural fever with and without actual infection).
Detailed description
Historically the diagnosis of chorioamnionitis (an infection of the membranes surrounding the fetus) for patients in labor has been made on the basis of multiple clinical variables such as maternal fever, fetal tachycardia, uterine tenderness, or foul smelling vaginal discharge. The diagnosis also takes into account a clinical picture consistent with risk factors such as prolonged labor and prolonged rupture of membranes. Since most of these findings are not specific, chorioamnionitis becomes the diagnosis of exclusion unless there is another explanation for the fever. Randomized studies have clearly shown that maternal antibiotics and neonatal septic work-ups are indicated once the diagnosis of chorioamnionitis has been made. Neonatal sepsis is a severe infection of the blood stream. Such policies have important implications for health care providers, on the impact of medical costs, and on the duration of hospital stay. This becomes especially true for the newborn that is transferred to the neonatal intensive care unit (NICU) for sepsis evaluation. Often times, these newborns are prophylactically treated with antibiotics based on the suspicion of an infection, while waiting for finalized blood culture results. Since newborn sepsis is such a difficult diagnosis to make, many more newborns are treated than actually have the disease and the length of their hospital stay may be significantly increased.
Over the past 15 years, both observational and randomized trials have observed an increase in maternal fever associated with epidural anesthesia in labor. These trials have shown increased ranges from 10 - 15% over baseline rates and an increased relative risk of 1.5 to 15 fold, and even up to 70 fold in one study, over the rates seen in women not receiving epidural anesthesia. After correcting for duration of labor and other confounding variables, these increases remained present. Since epidural fever is virtually impossible to distinguish from chorioamnionitis-related fever, these women are almost all treated with antibiotics and given the diagnosis of infection. This approach also has tremendous impact on the evaluation and care of the newborn. Two specific studies evaluated this impact on the neonate. Lieberman found that babies of mothers given epidural anesthesia were more likely to be evaluated for sepsis (34 vs. 9%) and treated with antibiotics (15 vs. 4%). Similarly, Philips found the same increase (25 vs. 16% and 19 vs. 11%). Both studies had very low rates of confirmed neonatal sepsis. On a national basis, the cost of this confusion nationally is tremendous.
There is one known way to distinguish between true chorioamnionitis in labor and non-infectious fever due to the epidural anesthesia. Gibbs and colleagues found that amniotic fluid aspirated from an intrauterine pressure catheter, a device commonly utilized for monitoring contractions in labor, could be used to accurately make the diagnosis of infection using gram stain and culture. More recently, many papers have shown that low glucose levels and elevated IL-6 in amniotic fluid were also accurate tests for infection. While these markers could in theory be used for distinguishing between epidural fever and true chorioamnionitis, most patients do not require such a device and this approach would not likely gain widespread favor. Alternatively, however, this approach could be used as a research tool in women who already have such a catheter in place to determine if there are additional non-invasive clinical or laboratory markers to distinguish one from the other.
Recently proteomic assessment has become an extremely effective tool in determining if there are certain markers for various diseases. Proteomics is the determination of the structure, function, and expression of all of the corresponding proteins that are encoded within the genome structure. It can also be defined as the "fingerprint" of a disease process. It involves running tandem mass spectometry on the fluid of interest. Such an approach could be extremely valuable both in determining whether the mother actually has chorioamnionitis and, if so, whether there are better markers for neonatal sepsis.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Women >18 years of age that present to labor and delivery and are in active labor.
Key inclusion criteria (8 listed)
- Nulliparous
- Maternal age > 18 years of age
- Estimated gestational age (EGA) > 36 0/7 weeks
- Active labor (> 4 cm dilated)
- Epidural anesthesia
Key exclusion criteria (3 listed)
- Multiparous
- Maternal age < 18 years of age
- External tocometer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2008.
- Background: PubMed 7033397Gibbs RS, Blanco JD, St Clair PJ, Castaneda YS. Quantitative bacteriology of amniotic fluid from women with clinical intraamniotic infection at term. J Infect Dis. 1982 Jan;145(1):1-8. doi: 10.1093/infdis/145.1.1.
- Background: PubMed 12011872Lieberman E, O'donoghue C. Unintended effects of epidural analgesia during labor: a systematic review. Am J Obstet Gynecol. 2002 May;186(5 Suppl Nature):S31-68. doi: 10.1067/mob.2002.122522.
- Background: PubMed 7566849Ramin SM, Gambling DR, Lucas MJ, Sharma SK, Sidawi JE, Leveno KJ. Randomized trial of epidural versus intravenous analgesia during labor. Obstet Gynecol. 1995 Nov;86(5):783-9. doi: 10.1016/0029-7844(95)00269-w.
- Background: PubMed 11704166Yancey MK, Zhang J, Schwarz J, Dietrich CS 3rd, Klebanoff M. Labor epidural analgesia and intrapartum maternal hyperthermia. Obstet Gynecol. 2001 Nov;98(5 Pt 1):763-70. doi: 10.1016/s0029-7844(01)01537-x.
- Background: PubMed 9041298Lieberman E, Lang JM, Frigoletto F Jr, Richardson DK, Ringer SA, Cohen A. Epidural analgesia, intrapartum fever, and neonatal sepsis evaluation. Pediatrics. 1997 Mar;99(3):415-9. doi: 10.1542/peds.99.3.415.
- Background: PubMed 12478449Chen KT, Ringer S, Cohen AP, Lieberman E. The role of intrapartum fever in identifying asymptomatic term neonates with early-onset neonatal sepsis. J Perinatol. 2002 Dec;22(8):653-7. doi: 10.1038/sj.jp.7210818.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael P Nageotte, MD principal investigator
Memorial Care
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Fever, run by MemorialCare at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Jun 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Christine Preslicka, Rn (562-933-2755, Cpreslicka@memorialcare.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00326521, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2008.