Prophylactic cosyntropin after unintentional dural puncture and incidence of post-dural puncture headache and epidural blood patch use: A retrospective cohort study (2019-2022).

BACKGROUND: Cosyntropin has been suggested to decrease the incidence of post-dural puncture headache (PDPH) by increasing the production of cerebrospinal fluid. This study examined the association of prophylactic cosyntropin administration with the incidence of PDPH and its management with an epidural blood patch after an unintentional dural puncture (UDP). METHODS: We conducted a retrospective cohort study of cases with UDP during placement of neuraxial labor analgesia. Per institutional practice and at the discretion of the anesthesiologist, intravenous cosyntropin 1 mg may be administered for PDPH prophylaxis. PDPH, time from UDP to cosyntropin administration, time to development of PDPH, and management with epidural blood patch(es) were recorded. RESULTS: Cosyntropin was administered in 164 of 234 (70%) cases with UDP. PDPH occurred 98/164 (60%) with cosyntropin and 45/70 (64%) without cosyntropin (p = 0.66). The PDPH adjusted incidence was 53% with cosyntropin and 62% without cosyntropin, difference 9% (95% CI -6% to 24%, p = 0.25). The adjusted epidural blood patch rate was 66% with cosyntropin and 78% without cosyntropin, difference of 12% (95% CI -5% to 28%, p = 0.17). CONCLUSIONS: Prophylactic cosyntropin following UDP was not associated with a significant decrease in PDPH rate or use of epidural blood patch for management of PDPH. There was no significant difference in the rate of adverse hyperglycemic or hypertensive events amongst those who did or did not receive cosyntropin.

Association of pain catastrophizing with labor pain and analgesia consumption in obstetrical patients.

INTRODUCTION: Pain catastrophizing is an exaggerated negative orientation to painful stimuli which in obstetric patients is associated with fear of overwhelming labor pain and negative pain-related outcomes. This study aimed to quantitatively examine the association of pain catastrophizing with maternal labor pain outcomes. METHODS: We conducted a prospective observational study of women admitted for a vaginal trial of labor. Subjects completed the 13-item Pain Catastrophizing scale (PCS) questionnaire (scored 0 to 52, higher scores representing greater catastrophizing). Pain was assessed at baseline and at request for neuraxial labor analgesia. Labor and postpartum pain intensity was assessed as the average area under the pain intensity by time curve. Pain at request for analgesia, labor pain, postpartum pain, analgesic consumption, and quality of recovery was compared between high (PCS ≥ 17) and low catastrophizing groups. RESULTS: Data from 138/157 (88%) subjects were included in the analysis. Median (IQR) pain scores at request for analgesia were 9 (8,10) and 8 (6,9), a difference of 1 (95% CI 0 to 2.5, P = 0.008) in high-catastrophizing and in low-catastrophizing groups, respectively. Adjusted pain during labor, postpartum pain and opioid analgesic use were not significantly different. High-catastrophizers reported less comfort, ability to mobilize and less control during hospitalization. Post-discharge there were no differences in pain or analgesic use. CONCLUSION: We did not observe greater labor or post-delivery pain or increased analgesic use in high-catastrophizing parturients. High catastrophizers reported greater pain when requesting analgesia, which is consistent with the role of catastrophizing in intensifying the experience of pain.

P6 acupressure versus sham acupressure for prevention of intraoperative nausea and vomiting during cesarean delivery under neuraxial anesthesia: a randomized controlled trial.

INTRODUCTION: Intraoperative and postoperative nausea and vomiting (IONV and PONV) are common during cesarean delivery (CD) with neuraxial anesthesia. Limited information exists on the antiemetic benefit of combined P6 acupoint stimulation with acupressure (P6 acupressure) and pharmacologic antiemetics on preventing IONV and PONV after CD. This study assessed the antiemetic efficacy of P6 acupressure compared to a non-P6 acupoint stimulation with acupressure (sham acupressure) in preventing IONV during CD. METHODS: We performed a randomized double-blinded trial comparing the efficacy of intraprocedural P6 acupressure versus sham acupressure in preventing IONV during CD after following the Society for Obstetric Anesthesia and Perinatology enhanced recovery recommendations. Subjects were instructed to apply additional pressure at the acupressure sites when they perceived nausea. The primary outcome was the incidence of IONV, and the secondary outcome was the need for rescue antiemetic treatment. RESULTS: Ninety-nine P6 acupressure and 100 sham acupressure subjects were studied. There was no difference in the incidence of intraoperative nausea (67%), vomiting (17%), emesis episodes, or the need for rescue antiemetics intraoperatively. There were also no differences in the incidence of PONV and antiemetic treatment from PACU to discharge. At discharge, 70% of respondents reported experiencing nausea, but only 10% reported it affected self-care. Approximately 50% of the patients in both groups were satisfied with acupressure therapy. CONCLUSION: P6 acupressure did not reduce the incidence of IONV or PONV when combined with antiemetic therapy per enhanced recovery recommendations. There does not appear to be sufficient evidence to support using P6 acupressure for IONV prevention.

Palliation of abdominal aortic aneurysms in the endovascular era.

OBJECTIVES: To establish outcome of patients with abdominal aortic aneurysm (AAA) deemed unfit for repair. DESIGN: Retrospective non-randomised study. MATERIALS AND METHODS: Identification of males with >5.5 cm or females with >5.0 cm AAA turned down for elective repair between 01/01/2006-24/07/2009 from a prospective database. Comorbidities, reasons for non-intervention, aneurysm size, survival, use of CPEX (cardio-pulmonary exercise) testing and cause of death were analysed. Although well-established at the time, patients unfit for open operation were not considered for endovascular repair. RESULTS: Seventy two patients were unsuitable for AAA repair. Aneurysm size ranged from 5.3 cm to 12 cm. Functional status, comorbidity and patient preference determined decision to palliate. Sixty percent of patients were alive at study close. Aneurysm rupture was cause of death in 46%. CPEX testing was performed in 54%, whose mortality was 28%, vs. 54% in the non-CPEX group (P < 0.05). Median survival of patients with 5.1-6.0 cm AAA was 44 months and 11% died of rupture. Between 6.1 and 7.0 cm median survival was 26 months and 20% died of rupture. However, with >7 cm aneurysms, survival was 6 months and 43% ruptured. CONCLUSION: Under half the deaths in our comorbid cohort were due to rupture. However, decision to palliate may be revisited as risk-benefit ratio changes with aneurysm expansion.

Virtual airway simulation to improve dexterity among novices performing fibreoptic intubation.

We developed a virtual reality software application (iLarynx) using built-in accelerometer properties of the iPhone(®) or iPad(®) (Apple Inc., Cupertino, CA, USA) that mimics hand movements for the performance of fibreoptic skills. Twenty novice medical students were randomly assigned to virtual airway training with the iLarynx software or no additional training. Eight out of the 10 subjects in the standard training group had at least one failed (> 120 s) attempt compared with two out of the 10 participants in the iLarynx group (p = 0.01). There were a total of 24 failed attempts in the standard training group and four in the iLarynx group (p < 0.005). Cusum analysis demonstrated continued group improvement in the iLarynx, but not in the standard training group. Virtual airway simulation using freely available software on a smartphone/tablet device improves dexterity among novices performing upper airway endoscopy.

A survey of United States obstetric anesthesiologists' perceived value of obstetric anesthesiology fellowship.

INTRODUCTION: Subspecialty training in obstetric anesthesiology is associated with improved patient outcomes and reduced anesthesia-related morbidity and mortality. Despite this, the demand for fellowship-trained obstetric anesthesiologists far exceeds the supply. This survey study aimed to evaluate the perceived value of obstetric anesthesiology subspecialty training on career trajectory, job satisfaction, quality of life, and job autonomy. METHODS: After Institutional Review Board approval, we conducted a cross-sectional study of fellowship-trained obstetric anesthesiologists in the United States of America. In March and April 2022, program directors of obstetric anesthesiology fellowships distributed an electronic survey link containing 29 multiple-choice questions to their program alumni. Survey content included respondent demographic characteristics, practice models, career information, and perceived value of an obstetric anesthesiology fellowship. RESULTS: We surveyed 217/502 (43%) fellowship-trained obstetric anesthesiologists with a response rate of 158/217 (73%). Most worked in urban, academic, and level IV perinatal health centers. The majority believed an obstetric anesthesiology fellowship was "extremely beneficial" (77%), enhanced quality of life (84%), improved the quality of patient care (99%), and was influential in helping obtain their first post-training job (86%). The perceived value of the fellowship included an enhanced career trajectory, a sense of purpose, improved job satisfaction, a sense of work community, lower burnout, involvement in maternal health initiatives, increased mentorship, and departmental leadership. CONCLUSION: In this survey study, fellowship-trained obstetric anesthesiologists perceived a positive impact of fellowship training on career trajectory, job protection and autonomy, quality of life, and job satisfaction. This information may be meaningful to trainees considering pursuing a fellowship and a career in obstetric anesthesiology.

Systemic metoclopramide to prevent postoperative nausea and vomiting: a meta-analysis without Fujii's studies.

Previous evidence suggested that 10 mg systemic metoclopramide is not effective to prevent postoperative nausea and/or vomiting (PONV) in patients receiving general anaesthesia. However, the evidence included data with questioned validity by the author Yoshitaka Fujii. The objective of the current study was to examine the effect of a systemic dose of 10 mg metoclopramide to prevent PONV. This quantitative systematic review was performed according to the PRISMA guidelines. A wide search was performed to identify randomized clinical trials that evaluated systemic 10 mg metoclopramide as a prophylactic agent to reduce PONV. Meta-analysis was performed using a random-effect model. Thirty trials evaluating the effect of 10 mg systemic metoclopramide in 3328 subjects on PONV outcomes were included. Metoclopramide reduced the incidence of 24 h PONV compared with control, odds ratio (OR) [95% confidence interval (CI)] of 0.58 (0.43-0.78), number needed to treat (NNT)=7.8. When evaluated as separate outcomes, metoclopramide also decreased the incidence of nausea over 24 h, OR (95% CI) of 0.51 (0.38-0.68), NNT=7.1, and vomiting over 24 h, OR (95% CI) of 0.51 (0.40-0.66), NNT=8.3. A post hoc analysis examining three studies with questioned validity performed by the author Yoshitaka Fujii that would meet criteria for inclusion in the current study did not demonstrate a significant benefit of metoclopramide compared with control on the incidence of 24 h PONV. Our findings suggest that metoclopramide 10 mg i.v. is effective to prevent PONV in patients having surgical procedures under general anaesthesia. Metoclopramide seems to be a reasonable agent to prevent PONV.

The association between allogeneic perioperative blood transfusion on tumour recurrence and survival in patients with advanced ovarian cancer.

OBJECTIVE: To evaluate the association between perioperative blood transfusion on the recurrence and survival of patient with advanced ovarian cancer. BACKGROUND: Cytoreductive surgery for ovarian cancer can be an extensive procedure often requiring allogeneic blood transfusions. Blood transfusions can have detrimental effects on immune function which can lead to a decrease in the organism ability to detect and destroy metastasis. METHODS: The study was a retrospective cohort investigation. Patients with advanced ovarian cancer (stage III) undergoing cytoreductive surgery were stratified by the need for perioperative blood transfusion. Allogeneic transfusions were non-leucodepleted. Primary outcome included time to recurrence and survival. Data were extracted from the gynaecology oncology database at Northwestern University. Times to event outcomes were evaluated by constructing Kaplan-Meyer curves and Cox regression. RESULTS: The charts of 136 subjects were evaluated. Seventy-six received blood transfusion. Median [95% confidence interval (CI)] time to recurrence for the non-transfusion group was longer, i.e. 17 (6-27) months, compared to 11 (8-14) months for the transfused group (P = 0.03). Median (95% CI) survival following surgery was longer in the non-transfused group, i.e. 58 (43-73) months, compared to 36 (28-44) months for the transfused group (P = 0.04). Cox regression showed that transfused subjects had shorter median times to recurrence and mortality after adjusting for age and tumour grade. CONCLUSIONS: There is an association between ovarian cancer recurrence and allogeneic perioperative blood transfusion in patients with advanced ovarian cancer undergoing cytoreductive surgery. These findings may have important implications in the perioperative management of those patients.

Dose ranging study on the effect of preoperative dexamethasone on postoperative quality of recovery and opioid consumption after ambulatory gynaecological surgery.

BACKGROUND: Glucocorticoids are commonly administered before ambulatory surgery, although their effects on quality of recovery are not well characterized. The purpose of this study was to evaluate the dose-dependent effects of dexamethasone on patient recovery using the Quality of Recovery 40 questionnaire (QoR-40) after ambulatory surgery. METHODS: This prospective, double-blind trial studied 106 female subjects undergoing outpatient gynaecological laparoscopy. Subjects were randomized to receive saline, dexamethasone 0.05 mg kg(-1) or dexamethasone 0.1 mg kg(-1) before induction. The primary outcome was global QoR-40 at 24 h. Postoperative pain, analgesic consumption, side-effects, and discharge time were also evaluated. RESULTS: Global median (IQR) QoR-40 after dexamethasone 0.1 mg kg(-1) 193 (192-195) was greater than dexamethasone 0.05 mg kg(-1) 179 (175-185) (P=0.004) or saline, 171 (160-182) (P<0.005). Median (IQR) morphine equivalents administered before discharge were 2.7 (0-6.3) mg after dexamethasone 0.1 mg kg(-1) compared with 5.3 (2.4-8.8) mg and 5.3 (2.7-7.8) mg after dexamethasone 0.05 mg kg(-1) and saline (P=0.02). Time to meet discharge criteria was 30 min shorter after dexamethasone 0.1 mg kg(-1) compared with saline (P=0.005). At 24 h, subjects receiving dexamethasone 0.1 mg kg(-1) had consumed less opioid analgesics, reported less sore throat, muscle pain, confusion, difficulty in falling asleep, and nausea compared with dexamethasone 0.05 mg kg(-1) and saline. CONCLUSIONS: Dexamethasone demonstrated dose-dependent effects on quality of recovery. Dexamethasone 0.1 mg kg(-1) reduced opioid consumption compared with dexamethasone 0.05 mg kg(-1), which may be beneficial for improving recovery after ambulatory gynaecological surgery.

Determination of residual antiplatelet activity of clopidogrel before neuraxial injections.

BACKGROUND: Guidelines recommend discontinuation of clopidogrel for 7 days before a neuraxial injection, while other directives suggest that 5 days might be adequate. We examined the time course of antiplatelet activity after clopidogrel discontinuation in patients undergoing epidural injections. METHODS: Thirteen patients were studied at baseline, 3, 5, and 7 days after discontinuation of clopidogrel. P(2)Y(12) determinations were performed using the VerifyNow(®) assay (Accumetrics, San Diego, CA, USA), and clot closure times with stimulation by collagen/epinephrine and collagen/adenosine diphosphate using the PFA-100(®) (Platelet Function Analyzer, Siemens Diagnostics, Deerfield, IL, USA). Repeated-measures ANOVA was used to evaluate P(2)Y(12) platelet reaction units, PFA-100 closure times, and per cent P(2)Y(12) inhibition values. Wilcoxon's signed-rank test was used to compare the frequencies of ≥30%, 11-29%, and ≤10% platelet inhibition between the baseline and subsequent sampling points after discontinuation of clopidogrel. RESULTS: On day 3 after clopidogrel discontinuation, two subjects had ≥30%, seven subjects had 11-29%, and four subjects had ≤10% platelet inhibition; the corresponding numbers were 0, 3, and 10 subjects on day 5 (P=0.04). There were no differences between the ≥30%, 11-29%, and <10% platelet inhibition groups between days 5 and 7 (0, 0, and 13 subjects, P=1.0). PFA-ADP closure times were normal throughout the study period except in one patient. CONCLUSIONS: These findings support the recommendation that discontinuation of clopidogrel for 5 days allows >70% of platelet function and might be adequate before a neuraxial injection is performed.

Detection of hypoventilation during deep sedation in patients undergoing ambulatory gynaecological hysteroscopy: a comparison between transcutaneous and nasal end-tidal carbon dioxide measurements.

BACKGROUND: Transcutaneous measurement of carbon dioxide (Tc(co(2))) provides a non-invasive estimation of arterial carbon dioxide (Pa(co(2))). Nasal capnography (Pe'(co(2))) is used to assess ventilation during monitored anaesthesia care (MAC) with sedation since it can readily detect apnoea. We compared the agreement between Tc(co(2)) and Pe'(co(2)) with Pa(co(2)) and the ability to detect hypercarbia in patients under deep sedation. METHODS: Forty healthy female subjects receiving deep sedation for hysteroscopy were studied. A Tc(co(2)) (TOSCA 500, Radiometer, Inc., Westlake, OH, USA) electrode was applied to the earlobe and Pe'(co(2)) capnography was monitored using nasal side-stream sampling. All subjects received oxygen (3 litre min(-1)). Subjects were evaluated at intervals using a modified Ramsay sedation score until they reached a score >or=5. Arterial blood gas values were compared with Tc(co(2)) and Pe'(co(2)) values. Bland-Altman, linear regression, and receiver operator characteristics analysis were performed. RESULTS: The mean (sd) absolute difference between the Tc(co(2)), Pe'(co(2)), and the Pa(co(2)) were 0.43 (0.35) and 1.06 (0.8) kPa, respectively (P=0.002). Tc(co(2)) demonstrated a mean bias (2 sd) of 0.23 (0.07-0.4) kPa with Pa(co(2)) compared with -0.93 (-1.24 to -0.63) kPa for Pe'(co(2)). One minute before blood sampling, the sensitivity of the Tc(co(2)) monitor for detecting Pa(co(2)) >6.65 kPa was greater than for Pe'(co(2)) (66.7% vs 33.3%, P<0.01). CONCLUSIONS: Tc(co(2)) demonstrated better agreement with Pa(co(2)) than Pe'(co(2)) for patients under MAC with deep sedation. Tc(co(2)) monitoring was more sensitive for detection of Pa(co(2)) >6.65 kPa than Pe'(co(2)).

Effect of companion presence on maternal satisfaction during neuraxial catheter placement for labor analgesia: a randomized clinical trial.

BACKGROUND: Neuraxial labor analgesia is frequently achieved after placing an epidural catheter under sterile conditions. There is no consensus on the risk versus benefit of allowing a parturient's companion to remain during the procedure. We sought to assess the effect of the presence of a companion on maternal satisfaction and anxiety during neuraxial catheter placement for labor analgesia. METHODS: Healthy nulliparous parturients planning to receive neuraxial labor analgesia after admission to labor, and who had a companion with them at the time of interview, were randomized to having a companion present or not present in the labor and delivery room during neuraxial catheter placement. Participants completed questionnaires to assess maternal anxiety, pain catastrophizing and health literacy. Satisfaction was scored on 5-point Likert scale (1- highly dissatisfied, 2- dissatisfied, 3- neutral, 4- satisfied, 5- highly satisfied). RESULTS: A total of 143 participants completed the study. The Wilcoxon-Mann-Whitney odds ratio for a random pair of satisfaction scores for a woman with her companion present compared with companion not present was 1.93 (95% CI 1.30 to 2.81, P=0.001). Anxiety scores were decreased following the procedure (P=0.39) in both groups. Eighty-nine percent of women randomized to companion not present would have preferred to have a companion present (P <0.001) compared with only one with their companion present who would have preferred her companion to be not present (P=0.99). CONCLUSION: Maternal satisfaction can be improved with the presence of a companion in the labor and delivery room at the time of neuraxial catheter placement for labor analgesia.

Anesthetic management of parturients with Arnold Chiari malformation-I: a multicenter retrospective study.

BACKGROUND: Consensus regarding the safest mode of delivery and anesthetic management for parturients with Arnold Chiari malformation-I (ACM-I) remains controversial. This study assessed their anesthetic management and reported anesthetic complications during hospitalization for delivery. METHODS: This was a multicenter, retrospective, cohort study of patients with ACM-I undergoing vaginal or cesarean delivery. Data were obtained from the electronic databases of four United States academic institutions using International Classification of Diseases (ICD) codes from 2007-2017 at three sites and 2004-2017 at one site. The primary outcome was anesthetic complications. RESULTS: Data were analyzed for 185 deliveries in 148 patients. Diagnosis of ACM-I was made prior to delivery in 147 (80%) cases. Pre-delivery neurosurgical consultation for management of ACM-I was performed in 53 (36%) patients. Pre-existing symptoms were recorded for 89 (48%) of the deliveries. Vaginal deliveries occurred in 80 (43%) cases, and 62 women (78%) received neuraxial labor analgesia. Cesarean delivery was performed in 105 (57%) cases, of which 70 women (67%) had neuraxial anesthesia and 34 (32%) received general anesthesia. Post-dural puncture headache was reported in three (2%) patients who had neuraxial anesthesia, and in two (12%) patients with syringomyelia. There was one (3%) reported case of aspiration pneumonia with general anesthesia. CONCLUSIONS: The findings suggest that anesthetic complications occur infrequently in patients with ACM-I regardless of the anesthetic management. Although institutional preference in anesthetic and obstetric care appears to drive patient management, the findings suggest that an individualized approach has favorable outcomes in this population.

Neuraxial labor analgesia is not an independent predictor of perineal lacerations after vaginal delivery of patients with intrauterine fetal demise.

INTRODUCTION: The role of neuraxial labor analgesia in perineal trauma following live births is controversial, and no studies have assessed the association in women delivering an intrauterine fetal demise. We evaluated the relationship between neuraxial labor analgesia and perineal laceration in these patients. METHODS: This was a retrospective case-control study of women with a diagnosis of fetal death after 20weeks of gestation, a vaginal delivery, and an Apgar score of 0 at delivery, during the period from January 2007 through December 2015. The presence of a perineal laceration and its severity, graded from grade I to IV based on the 2014 American College of Obstetricians and Gynecologists guidelines, was recorded. RESULTS: A total of 329/422 (78%) patients received neuraxial, and 93/422 (22%) non-neuraxial, labor analgesia. A perineal laceration occurred in 23% in the neuraxial versus 10% in the non-neuraxial analgesia group, a difference of 13% (95% CI of difference 4% to 20%, P=0.005). After adjusting for confounder bias, greater birthweight (OR 4.22, 95% CI 3.00 to 5.92, P<0.001) and lower parity (OR 0.44, 95% CI 0.24 to 0.82, P=0.009), but not neuraxial analgesia (OR 1.29, 95% CI 0.47 to 3.57, P=0.61) were independent predictors of perineal laceration. The maintenance concentration of bupivacaine did not affect the rate of perineal injury. CONCLUSIONS: Neuraxial labor analgesia does not appear to be an independent risk for a perineal laceration in patients with intrauterine fetal demise. Our data suggests that the use of neuraxial analgesia should not raise concern about increased rates of perineal injury.

Maternal sedation during scheduled versus unscheduled cesarean delivery: implications for skin-to-skin contact.

BACKGROUND: Early maternal skin-to-skin contact confers numerous benefits to the newborn, but maternal sedation during cesarean delivery could have safety implications for early skin-to-skin contact in the operating room. We compared patient-reported and observer-assessed levels of sedation during unscheduled and scheduled cesarean deliveries. METHODS: Laboring women undergoing unscheduled cesarean delivery with epidural anesthesia, and scheduled cesarean delivery with spinal anesthesia were enrolled. Sedation levels, measured using patient-reported (1=least sedated to 10=most sedated) and observer-assessed (0=most sedated to 5=least sedated) scales, were evaluated at baseline and 15, 30, 45, and 60min following a T4 sensory level. The primary outcomes were patient-reported sedation at 45min and the areas under the sedation curves. RESULTS: Patient-reported levels of sedation were greater at 45min in laboring women undergoing unscheduled (median 7.5, IQR 5-9) versus scheduled cesarean delivery (median 4, IQR 3-6) (difference in medians 3.5, 99% CI 0 to 5). Observer-assessed sedation was not different between groups. The area under the time curve for patient-reported sedation was greater in the unscheduled group, median difference 162 score min (95% CI 52 to 255). The area under the time curve for observer-assessed sedation was greater in the unscheduled group, median difference 26 score min (99% CI 0 to 41). Times to skin-to-skin contact and breastfeeding were not different. CONCLUSIONS: Women undergoing unscheduled cesarean deliveries are more sedated than women undergoing scheduled cesarean deliveries. Skin-to-skin protocols for cesarean deliveries must consider maternal sedation and anesthesiologists should use sedating medications judiciously.

A porcine model of peritonitis and bacteremia simulates human septic shock.

Cardiovascular responses to systemic bacteremia were evaluated in a pre-instrumented, conscious pigs. Basal observations were obtained 5-7 days after instrumentation. On the next day, Escherichia coli 0111.B4 (1.1 to 33 x 10(9) CFU/kg)-laden fibrin clots were implanted intraperitoneally. Nonsurvivors (9/18) demonstrated rapid cardiovascular decompensation. Survivors (9/18) demonstrated significant cardiovascular injury, which was reversed by 5-7 days postimplant. Cardiac inotropicity was significantly reduced in this period, but recovered by day 7. Circulating myocardial depressant substance activity (assayed by serum-induced depression of beating neonatal rat myocytes) was present on days 1-4 of bacteremia and recovered to basal values on day 6. No clinical or cardiovascular changes were seen in pigs implanted with sterile clots (n = 4). These data demonstrate that implantation of bacteria-laden fibrin clots in pigs induces cardiovascular alterations that mimic responses seen in human sepsis.

Randomized, blinded, placebo-controlled trial of tissue factor pathway inhibitor in porcine septic shock.

This study tested the hypothesis that tissue factor pathway inhibitor (TFPI) would improve mortality and morbidity evoked by peritonitis-induced bacteremia in pigs. Secondarily, it sought to determine if TFPI treatment would attenuate cardiodynamic abnormalities produced by this septic model. 32 pigs were chronically instrumented with intracardiac transducers to measure left ventricular pressure and diameter, pulmonary and aortic pressures, and cardiac output. At least 5 days after surgery to implant transducers, basal cardiovascular readings and blood samples were obtained. Using a randomized, blinded study design, either purified, reconstituted TFPI (1 mg/kg bolus, 10 mg/kg/min for 48 h), placebo (arginine buffer), or saline was administered to pigs immediately after Escherichia coli 0111.B4 (3.0-11 x 10(9) colony-forming U/kg)-laden fibrin clots were implanted intraperitoneally, producing peritonitis and bacteremia. Pigs did not receive antibiotics or supportive therapy. No significant differences in primary or secondary endpoints were noted between the arginine and saline groups, so these data were combined into a control group (N = 20). 5 of 12 TFPI pigs survived (42%), while 5 of 20 control pigs survived (25%); this difference was not significant (p = .714, Fisher's exact test). TFPI treatment augmented cardiac output in surviving pigs, but did not affect any other cardiovascular performance variable (heart rate, % diameter shortening, or systemic and pulmonary vascular resistance). In controls, peritonitis induced rapid increase in plasma tumor necrosis factor-alpha (428 +/- 771 to 5,933 +/- 559 pg/mL at 2 h) and interleukin-8 (180 +/- 153 to 1,393 +/- 145 pg/mL at 2 h). TFPI treatment significantly attenuated cytokine responses to sepsis, reducing peak tumor necrosis factor-alpha to 2,103 +/- 813 pg/mL and reducing peak interleukin-8 levels to 534 +/- 211 pg/mL at 2 h (p < .05, Tukey test, two-way ANOVA). In conclusion, TFPI treatment attenuated important mediator components of the inflammatory response but did not provide significant survival benefit.

Differential effects of advanced age on neurologic and cardiac risks of coronary artery operations.

Two thousand patients undergoing coronary artery bypass grafting with cardiopulmonary bypass were prospectively studied to compare the influence of age on the incidence of neurologic, cardiac, and other complications. Postoperative neurologic events were found in 56 (2.8%) patients, with an incidence in patients > or = 75 years (8.9%) more than twice that of patients 65 to 74 (3.6%) and nine times larger than in patients < 65 (0.9%). Cardiac complications did not differ between age groups except for low cardiac output state, which occurred 1.7 times more frequently in patients > or = 75 years compared with those < 65. Patients with postoperative neurologic events had a ninefold increase in mortality--35.7% versus 4.0%. Logistic regression analysis demonstrate the most important predictors of a postoperative neurologic event to be age, preoperative neurologic abnormality, recent myocardial infarction, and duration of cardiopulmonary bypass. The risk of neurologic complications increases disproportionately to the risk of cardiac complications in the elderly undergoing coronary artery bypass grafting with cardiopulmonary bypass. Despite neurologic improvement (32 of 56 patients), a postoperative neurologic event was second only to low cardiac output state as the postoperative complication most highly associated with in-hospital death. These results are important for decisions regarding selection of candidates for coronary artery bypass grafting and for prediction of surgical outcome.