Guro Grindheim

Changes in blood pressure during healthy pregnancy: a longitudinal cohort study.

Objective: To study longitudinally changes in blood pressure (BP) and heart rate (HR) during healthy pregnancies and to evaluate the influence of parity, pregestational overweight, and excessive weight gain. Methods: A prospective longitudinal cohort study of 57 healthy white women with singleton pregnancies. BP and HR were measured repeatedly at gestational age 14–16 weeks, 22–24 weeks, 30–32 weeks, 36 weeks, and 6 months postpartum using both an oscillometric measurement device (Dinamap) and finger arterial pressure (Finometer PRO). Results: SBP, DBP, and mean arterial pressure (MAP) reached a statistically significant trough at gestational age 22–24 weeks using both measurement devices. When compared with the nonpregnant measurement, SBP at gestational age 22–24 weeks was 6.2 mmHg [95% confidence interval (95% CI) 1.3–11.2] lower measured by Finometer and 7.2 mmHg (95% CI 4.2–10.1) lower measured by Dinamap. DBP and MAP were 8.9 mmHg (95% CI 4.6–13.2) and 9.8 mmHg (95% CI 5.3–14.2) lower measured by Finometer. Measured by Dinamap, DBP and MAP were 4.5 mmHg (95% CI 1.7–7.3) and 5.4 mmHg (95% CI 2.8–7.9) lower at gestational age 22–24 weeks when compared with the nonpregnant state. SBP was significantly higher in women with pregestational BMI at least 25 kg/m2 with both measurement devices (both P < 0.05). There were no differences in SBP, DBP, or MAP depending on parity or excessive weight gain. Conclusion: BP measured repeatedly by two different noninvasive devices during pregnancy and postpartum showed a statistically significant drop in mid-pregnancy, followed by a progressive increase until term.

Changes in blood pressure and cardiac output during cesarean delivery: the effects of oxytocin and carbetocin compared with placebo.

Background:Little is known about maternal hemodynamics after Cesarean delivery. Uterine contractions may increase cardiac output. Oxytocin is the first-line treatment for uterine atony, although the effects of the long-acting oxytocin analogue carbetocin are comparable with that of oxytocin. The authors analyzed the effects of i.v. oxytocin 5 U, carbetocin 100 µg, and placebo on hemodynamics, uterine tone, adverse events, and blood loss after Cesarean delivery. Methods:This was a randomized, double-blinded, placebo-controlled, parallel-group comparison of carbetocin and oxytocin after elective Cesarean delivery of singletons under spinal anesthesia (n = 76). Continuously measured invasive systolic arterial pressure was the primary outcome measure. Results:The mean systolic arterial pressure decrease was 28 mmHg (95% CI, 22–34) after oxytocin and 26 mmHg (95% CI, 20–31) after carbetocin. The decrease was greatest after 80 (95% CI, 71–89) and 63 s (95% CI, 55–72), respectively (P = 0.006). The differences were nearly undetectable after 2.5 min, although the effect of carbetocin was slightly greater than placebo (P < 0.001). The group differences in systolic arterial pressure decreased over 5 min and were gone at 1 h. Heart rate and cardiac output increased in all three groups. Stroke volume increased after oxytocin and carbetocin but was unchanged after placebo. Conclusions:The hemodynamic side effects of oxytocin 5 U and carbetocin 100 µg were comparable. The lack of an increase in stroke volume in the placebo group challenges the theory that uterine contraction causes autotransfusion of uterine blood, leading to an increase in preload.

Altered maternal left ventricular contractility and function during normal pregnancy.

To evaluate maternal left ventricular (LV) systolic and diastolic function during normal pregnancy by non‐invasive measures of LV contractility incorporating loading conditions.

Increased Arterial Stiffness in Pre-eclamptic Pregnancy at Term and Early and Late Postpartum: A Combined Echocardiographic and Tonometric Study

BACKGROUND Pre-eclampsia (PE) is characterized by hypertension and proteinuria, and complicates from 3%-10% of all pregnancies. The hemodynamic pathophysiology of the heart and systemic arteries in pre-eclamptic patients has not been well described. We therefore performed a comprehensive comparison of the systemic arterial properties at term and at 6 months postpartum in women with PE and in women with normal pregnancy (NP) and in nonpregnant women with a previous pre-eclamptic pregnancy (PPEP). METHODS The comparison included 40 patients with PE, 40 others with a PPEP (at 3.5±1.0 years postpartum), and 65 women who had had an NP. Noninvasive estimates of blood flow and pressure in the aortic root were made with echocardiography and calibrated right subclavian artery pulse traces obtained through tonometry. Total arterial compliance (C), arterial elastance (Ea), characteristic impedance (Z0), and peripheral arterial resistance (R) were estimated both through the use of a three-element Windkessel model and Fourier analysis of pressure and flow data. RESULTS At term, Z0, Ea, and R were higher by 37%, 25%, and 23%, respectively (all P < 0.05) in women with PE than in those with an NP, and C was lower by 12% (P < 0.05). The values of Z0, Ea, and R remained elevated at 6 months postpartum in women who had had PE, and were also elevated in those with a PPEP, as compared to their values in NP. CONCLUSIONS Our results demonstrate that pre-eclamptic pregnancies are characterized by a higher resistance throughout the arterial system. The altered arterial properties (Ea, Z0, and R) persisted at 6 months after PE and were also elevated at 3 years postpartum in women with a PPEP, indicating that PE induces long-standing cardiovascular disturbances.

Changes in pulmonary function during pregnancy: a longitudinal cohort study

Please cite this paper as: Grindheim G, Toska K, Estensen M, Rosseland L. Changes in pulmonary function during pregnancy: a longitudinal cohort study. BJOG 2012;119:94–101.

Early bedside detection of ischemia and rejection in liver transplants by microdialysis

This study was performed to explore whether lactate, pyruvate, glucose, and glycerol levels sampled via microdialysis catheters in the transplanted liver could be used to detect ischemia and/or rejection. The metabolites were measured at the bedside every 1 to 2 hours after the operation for a median of 10 days. Twelve grafts with biopsy‐proven rejection and 9 grafts with ischemia were compared to a reference group of 39 grafts with uneventful courses. The median lactate level was significantly higher in both the ischemia group [5.8 mM (interquartile range = 4.0‐11.1 mM)] and the rejection group [2.1 mM (interquartile range = 1.9‐2.4 mM)] versus the reference group [1.5 mM (interquartile range = 1.1‐1.9 mM), P < 0.001 for both]. The median pyruvate level was significantly increased only in the rejection group [185 μM (interquartile range = 155‐206 μM)] versus the reference group [124 μM (interquartile range = 102‐150 μM), P < 0.001], whereas the median lactate/pyruvate ratio and the median glycerol level were increased only in the ischemia group [66.1 (interquartile range = 23.9‐156.7) and 138 μM (interquartile range = 26‐260 μM)] versus the reference group [11.8 (interquartile range = 10.6‐13.6), P < 0.001, and 9 μM (interquartile range = 9‐24 μM), P = 0.002]. Ischemia was detected with 100% sensitivity and greater than 90% specificity when a positive test was repeated after 1 hour. In 3 cases of hepatic artery thrombosis, ischemia was detected despite normal blood lactate levels. Consecutive pathological measurements for 6 hours were used to diagnose rejection with greater than 80% sensitivity and specificity at a median of 4 days before the activity of alanine aminotransferase, the concentration of bilirubin in serum, or both increased. In conclusion, bedside measurements of intrahepatic lactate and pyruvate levels were used to detect ischemia and rejection earlier than current standard methods could. Discrimination from an uneventful patient course was achieved. Consequently, intrahepatic graft monitoring with microdialysis may lead to the earlier initiation of graft‐saving treatment. Liver Transpl, 2012.

Inflammatory markers sampled by microdialysis catheters distinguish rejection from ischemia in liver grafts

Rejection and ischemia are serious complications after liver transplantation. Early detection is mandatory, but specific markers are largely missing, particularly for rejection. The objective of this study was to explore the ability of microdialysis catheters inserted in liver grafts to detect and discriminate rejection and ischemia through postoperative measurements of inflammatory mediators. Microdialysis catheters with a 100‐kDa pore size were inserted into 73 transplants after reperfusion. After the studys completion, complement activation product 5a (C5a), C‐X‐C motif chemokine 8 (CXCL8), CXCL10, interleukin‐1 (IL‐1) receptor antagonist, IL‐6, IL‐10, and macrophage inflammatory protein 1β were analyzed en bloc in all grafts with biopsy‐confirmed rejection (n = 12), in grafts with vascular occlusion/ischemia (n = 4), and in reference grafts with a normal postoperative course of circulating transaminase and bilirubin levels (n = 17). The inflammatory mediators were elevated immediately after graft reperfusion and decreased toward low, stable values during the first 24 hours in nonischemic grafts. In grafts suffering from rejection, CXCL10 increased significantly (P = 0.008 versus the reference group and P = 0.002 versus the ischemia group) 2 to 5 days before increases in circulating alanine aminotransferase and bilirubin levels. The area under the receiver operating characteristic curve was 0.81. Grafts with ischemia displayed increased levels of C5a (P = 0.002 versus the reference group and P = 0.008 versus the rejection group). The area under the curve was 0.99. IL‐6 and CXCL8 increased with both ischemia and rejection. In conclusion, CXCL10 and C5a were found to be selective markers for rejection and ischemia, respectively. Liver Transpl, 2012.

Clinical experience with microdialysis catheters in pediatric liver transplants.

Ischemic vascular complications and rejection occur more frequently with pediatric liver transplants versus adult liver transplants. Using intrahepatic microdialysis catheters, we measured lactate, pyruvate, glucose, and glycerol values at the bedside for a median of 10 days in 20 pediatric liver grafts. Ischemia (n = 6), which was defined as a lactate level > 3.0 mM and a lactate/pyruvate ratio > 20, was detected without a measurable time delay with 100% sensitivity and 86% specificity. Rejection (n = 8), which was defined as a lactate level > 2.0 mM and a lactate/pyruvate ratio < 20 lasting for 6 or more hours, was detected with 88% sensitivity and 45% specificity. With additional clinical criteria, the specificity was 83% without a decrease in the sensitivity. Rejection was detected at a median of 4 days (range = 1‐7 days) before alanine aminotransferase increased (n = 5, P = 0.11), at a median of 4 days (range = 2‐9 days) before total bilirubin increased 25% or more (n = 7, P = 0.04), and at a median of 6 days (range = 4‐11 days) before biopsy was performed (n = 8, P = 0.05). In conclusion, microdialysis catheters can be used to detect episodes of ischemia and rejection before current standard methods in pediatric liver transplants with clinically acceptable levels of sensitivity and specificity. The catheters were well tolerated by the children, and no major complications related to the catheters were observed. Liver Transpl 19:305–314, 2013.

Elevated inflammatory markers in preeclamptic pregnancies, but no relation to systemic arterial stiffness

OBJECTIVES To investigate if circulating markers of systemic and vascular inflammation are associated with systemic arterial properties at term and 6months post-partum in women with preeclampsia (PE) and normal pregnancy (NP). STUDY DESIGN Longitudinal, sampling at term and 6months post-partum in 34 women (32±6years) with PE and 61 women (32±5years) with NP. MAIN OUTCOME MEASURES Circulating markers related to systemic and vascular inflammation were measured by enzyme immune-assay. Systemic arterial properties were estimated by Doppler (transthoracic echocardiography) and calibrated right subclavian artery pulse traces. RESULTS CXCL16, soluble tumor necrosis factor receptor type 1 (sTNF-R1), monocyte chemoattractant peptide 1, pentraxin 3 and soluble vascular adhesion molecule 1 (sVCAM-1) were elevated at term in PE, and sTNF-R1 remained elevated 6months post partum compared to NP. However, apart from a negative correlation between mean arterial pressure and sTNF-R1 and sVCAM-1 at term, no associations between systemic and vascular inflammatory markers and systemic arterial properties as reflected by characteristic impedance and arterial elastance, representing proximal aortic stiffness and effective arterial elastance, were found at any time point. CONCLUSIONS Preeclamptic pregnancies are characterized by increased circulating levels of systemic and vascular inflammatory markers. However, these are not associated with systemic arterial properties at term or 6months post partum.

Systemic arterial response and ventriculo–arterial interaction during normal pregnancy

BACKGROUND During normal pregnancy (NP), cardiac output (CO) increases, and blood pressure and systemic vascular resistance are reduced. We wanted to evaluate systemic arterial properties and interaction between the left ventricle (LV) and systemic arteries during NP. The role of systemic arteries and their interaction with LV-function in this hemodynamic response, lack description. METHODS We used noninvasive methods to study 65 healthy women (32 ± 5 years) with NP repeatedly at gestational weeks 14-16, 22-24, 36, and 6 months postpartum (PP). Aortic root pressure and flow were obtained by calibrated right subclavian artery pulse traces and aortic annular Doppler flow recordings. Arterial properties were described by estimates of total arterial compliance (C), proximal aortic stiffness (characteristic impedance (Z(0))), arterial elastance (Ea), and peripheral arterial resistance (R). Ventriculo-arterial coupling (VAC) was characterized by the ratio between arterial (E(a)I) and LV (E(LV)I) elastance index. RESULTS During NP, CO increased by 20% due to increased heart rate and stroke volume. Mean arterial pressure was reduced by 10% (P < 0.001) as compared to 6 months PP. R was reduced by 5% (P < 0.01), Z(0) trended lower and C higher. E(a)I decreased (P < 0.01) and E(LV)I was reduced to a higher extent resulting in 29% increase of E(a)I/E(LV)I during NP (P < 0.01). CONCLUSIONS During NP there is an increase in CO, and decrease in blood pressure and R whereas central aortic properties are less altered. The increased VAC index (E(a)I/E(LV)I) during NP indicates a decrease in LV-function not fully compensated for by vascular adaptation.