The importance of concomitant mitral regurgitation for estimates of mitral valve area by pressure half time in patients with chronic rheumatic heart disease.

AIMS: Aim was to study how concomitant mitral regurgitation (MR) assessed by qualitative and quantitative methods influence mitral valve area (MVA) calculations by the pressure half time method (MVAPHT) compared to reference MVA (planimetry) in patients with rheumatic heart disease. METHODS AND RESULTS: In 72 patients with chronic rheumatic heart disease, MVAPHT was calculated as 220 divided by the pressure half time of the mitral early inflow Doppler spectrum. Direct measurement by planimetry was used as reference MVA and was mean (SD) 0.99 (0.69-1.99) cm2. Concomitant MR was present in 82%. MR severity was assessed qualitatively in all, semi-quantitatively by measuring the vena contracta width in 58 (81%), and quantitatively by calculation of the regurgitant volume in 28 (39%). MVA was significantly underestimated by MVAPHT, with increasing MR. In regression analyses MVAPHT underestimated MVA by 0.19 cm2 per higher grade of MR severity in qualitative assessment, and by 0.12-0.13 cm2 per mm larger vena contracta width and 10 ml larger regurgitant volume, respectively. The presented associations were more evident when i) MR severity was quantified compared to qualitative assessment and ii) reference measurements were made by three-dimensional transoesophageal recordings compared to transthoracic recordings. CONCLUSION: MVAPHT underestimated mitral valve area compared to planimetry in patients with MS and concomitant MR. This study highlights the importance of taking the MR severity into account when evaluating MVA based on the PHT method. Direct measurements should be included in clinical decision making.

Short-term outcome after open-heart surgery for severe chronic rheumatic heart disease in a low-income country, with comparison with an historical control group: an observational study.

OBJECTIVES: Rheumatic heart disease (RHD) is a major burden in low-income and middle-income countries (LMICs). Cardiac surgery is the only curative treatment. Little is known about patients with severe chronic RHD operated in LMICs, and challenges regarding postoperative follow-up are an important issue. At Tikur Anbessa Specialised Hospital, Addis Ababa, Ethiopia, we aimed to evaluate the course and 12-month outcome of patients with severe chronic RHD who received open-heart surgery, as compared with the natural course of controls waiting for surgery and undergoing only medical treatment. METHODS: Clinical data and outcome measures were registered in 46 patients operated during five missions from March 2016 to November 2019, and compared with the first-year course in a cohort of 49 controls from the same hospital's waiting list for surgery. Adverse events were death or complications such as stroke, other thromboembolic events, bleeding, hospitalisation for heart failure and infectious endocarditis. RESULTS: Survival at 12 months was 89% and survival free from complications was 80% in the surgical group. Despite undergoing open-heart surgery, with its inherent risks, outcome measures of the surgical group were non-inferior to the natural course of the control group in the first year after inclusion on the waiting list (p≥0.45). All except six surgical patients were in New York Heart Association class I after 12 months and 84% had resumed working. CONCLUSIONS: Cardiac surgery for severe chronic RHD is feasible in LMICs if the service is structured and planned. Rates of survival and survival free from complications were similar to those of controls at 12 months. Functional level and resumption of work were high in the surgical group. Whether the patients who underwent cardiac surgery will have better long-term prognosis, in line with what is known in high-income countries, needs to be evaluated in future studies.

Is the use of hydroxyethyl starch as priming solution during cardiac surgery advisable? A randomized, single-center trial.

INTRODUCTION: The use of cardiopulmonary bypass (CPB) leads to increased fluid filtration and edema. The use of artificial colloids to counteract fluid extravasation during cardiac surgery is controversial. Beneficial effects on global fluid loading, leading to better cardiac performance and hemodynamics, have been claimed. However, renal function and coagulation may be adversely affected, with unfavorable impact on outcome following cardiac surgery. METHODS: Forty patients were randomly allocated to study groups receiving either acetated Ringer's solution (CT group) or hydroxyethyl starch (HES group, Tetraspan®) as CPB priming solution. Fluid balance, bleeding and hemodynamics, including cardiac output, were followed postoperatively. The occurrence of acute kidney injury was closely registered. RESULTS: Two patients were excluded from further analyzes due to surgical complications. Fluid accumulation was attenuated in the HES group (3374 (883) ml) compared with the CT group (4328 (1469) ml) (p=0.024). The reduced perioperative fluid accumulation was accompanied by an increased cardiac index immediately after surgery (2.7 (0.4) L/min/m2 in the HES group and 2.1 (0.3) L/min/m2 in the CT group (p<0.001)). No increase in bleeding could be demonstrated in the HES group. Three patients, all of them in the HES group, experienced acute kidney injury postoperatively. CONCLUSIONS: CPB priming with HES solution lowers fluid loading during bypass and improves cardiac function in the early postoperative period. The manifestation of acute kidney injury exclusively in the HES group of patients raises doubts about the use of HES products in conjunction with cardiac surgery. ( https://clinicaltrials.gov/ct2/show/NCT01511120 ).

Surface cooling versus core cooling: comparative studies of microvascular fluid- and protein-shifts in a porcine model.

OBJECTIVE: To describe how surface cooling compared with core cooling influences fluid and protein distribution, vascular capacity and hemodynamic variables. METHODS: 14 anesthetized piglets were, following 60 min normothermic stabilization, randomly cooled by surface cooling (ice-sludge) (n=7) or core cooling (endovascular cooling) (n=7) to about 28 degrees C. Fluid balance, hemodynamic variables, colloid osmotic pressures (plasma/interstitial fluid), hematocrit, serum-albumin and -protein concentrations, intracranial pressure (ICP) and cerebral metabolic markers of ischemia were measured. Fluid shifts and changes in albumin and protein masses were calculated. At the end total tissue water content was assessed and compared with a normothermic control group. RESULTS: Both cooling modes induced an increase in fluid extravasation rate from 33.9 (31.9) and 27.8 (28.0) to 109.0 (16.5) (P=0.006) and 95.6 (29.1) ml/kg/min x 10(-3) (P=0.024) in the surface-cooled and core-cooled groups, respectively. Albumin extravasation was reflected by a significant drop in the albumin mass from 148.8 (11.7) to 111.4 (10.3) (P=0.000) and from 163.4 (27.8) to 136.8 (19.0) g/kg x 10(-2) (P=0.001) in the surface-cooled and core-cooled animals, respectively. Similar findings were obtained concerning serum-protein masses. The total tissue water content increased in most organs including brain in both study groups compared with a control. ICP and cerebral metabolic markers remained normal in both groups. CONCLUSION: Rapid lowering of body core temperature results in extravasation of water and proteins. The amount of extravated fluid and proteins is similar either cooling is a result of surface cooling or core cooling. Cold-induced fluid extravasation is associated with edema in most tissues including brain.

Fluid overload during cardiopulmonary bypass is effectively reduced by a continuous infusion of hypertonic saline/dextran (HSD).

OBJECTIVE: Cardiopulmonary bypass (CPB) is associated with fluid overload. We examined how a continuous infusion of hypertonic saline/dextran (HSD) influenced fluid shifts during CPB. MATERIALS AND METHODS: Fourteen animals were randomized to a control-group (CT-group) or a hypertonic saline/dextran-group (HSD-group). Ringer's solution was used as CPB-prime and as maintenance fluid at a rate of 5 ml/kg/h. In the HSD group, 1 ml/kg/h of the maintenance fluid was substituted with HSD. After 60 min of normothermic CPB, hypothermic CPB was initiated and continued for 90 min. Fluid was added to the CPB-circuit as needed to maintain a constant level in the venous reservoir. Fluid balance, plasma volume, total tissue water (TTW), intracranial pressure (ICP) and fluid extravasation rates (FER) were measured/calculated. RESULTS: In the HSD-group the fluid need was reduced with 60% during CPB compared with the CT-group. FER was 0.38(0.06) ml/kg/min in the HSD-group and 0.74 (0.16) ml/kg/min in the CT-group. TTW was significantly lower in the heart and some of the visceral organs in the HSD-group. In this group ICP remained stable during CPB, whereas an increase was observed in the CT-group (p<0.01). CONCLUSIONS: A continuous infusion of HSD reduced the fluid extravasation rate and total fluid gain during CPB. TTW was reduced in the heart and some visceral organs. During CPB ICP remained normal in the HSD-group, whereas an increase was present in the CT-group. No adverse effects were observed.

Low perfusion pressure during CPB may induce cerebral metabolic and ultrastructural changes.

BACKGROUND: Recently we reported on cerebral metabolic changes suggesting ischemia in piglets during nitroprusside-induced low-pressure CPB. We here investigated whether a mean arterial pressure (MAP) of 40-45 mmHg could provoke similar changes by a NO-independent intervention. METHODS: Piglets underwent 60 minutes normothermic followed by 90 minutes hypothermic CPB. The LP-group (n=8) had MAP of 40-45 mmHg by phentolamine while the HP-group (n=8) had MAP of 60-80 mmHg by norepinephrine. Cerebral glucose, lactate, pyruvate and glycerol were determined. In the last two animals of each group, cerebral tissue was examined by electron microscopy. RESULTS: Cerebral lactate was higher in the LP-group than the HP-group during normothermic CPB. Compared with baseline, cerebral glucose of the LP-group decreased whereas lactate/pyruvate-ratio, lactate and glycerol-concentrations increased during normothermic CPB. In the HP-group these parameters remained unchanged. Electron microscopy showed 31.2% and 8.3% altered mitochondria in the cortical micrographs taken from the LP- and the HP-group, respectively (p<0.001). CONCLUSION: MAP below 45 mmHg during CPB was associated with cerebral biochemical and morphological changes consistent with anaerobic metabolism and subcellular injury.

Elevated flow rate during cardiopulmonary bypass is associated with fluid accumulation.

OBJECTIVE: High flow rates during cardiopulmonary bypass are assumed to increase fluid accumulation. This study aimed to determine whether two different flow rates during cardiopulmonary bypass alter the intraoperative fluid balance and extravasation rate. METHODS: Sixteen pigs underwent 60 minutes of normothermic bypass, followed by 90 minutes of hypothermic bypass. A high-flow group (HF group, n = 8) had a cardiopulmonary bypass flow rate of 110 mL x kg(-1) x min(-1) and a low-flow group (LF group, n = 8) had a rate of 80 mL x kg(-1) x min(-1). Blood chemistry, hemodynamic parameters, plasma and interstitial colloid osmotic pressure, net fluid balance, plasma volume, fluid extravasation rate, and total tissue water content were measured or calculated. Results are presented as mean (standard deviation). RESULTS: The average net fluid balance during cardiopulmonary bypass was 1.02 (0.25) and 0.73 (0.23) mL x kg(-1) x min(-1) in the HF group and LF group, respectively (P < .05). The average fluid extravasation rate was 0.98 (0.22) and 0.77 (0.22) mL x kg(-1) x min(-1) in the HF group and the LF group (P = .07). Total water content was higher in the kidneys (P < .05) and tended to be higher in the lungs (P = .05), liver (P = .07), and brain (P = .07) of the HF group than in those of the LF group. The between-group differences in net fluid balance and fluid extravasation rate were present during the first 30 minutes of normothermic cardiopulmonary bypass. Thereafter, the values stabilized and remained similar in the two groups. Plasma volume and systemic vascular resistance differed between the groups. CONCLUSION: Cardiopulmonary bypass flow rate of 110 mL x kg(-1) x min(-1) was associated with higher positive net fluid balance and fluid extravasation rate than 80 mL x kg(-1) x min(-1). The effect was mainly observed in the initial phase of cardiopulmonary bypass.

Intraoperative fluid balance during cardiopulmonary bypass: effects of different mean arterial pressures.

INTRODUCTION: This study investigated whether two levels of mean arterial pressure (MAP) during cardiopulmonary bypass did influence per-operative fluid shifts. METHODS: Sixteen pigs underwent 60 minutes of normothermic cardiopulmonary bypass (CPB) followed by 90 minutes of hypothermic CPB. Eight animals had a MAP of 60-80mmHg by norepinephrine (HP group). Another 8 animals had a MAP of 40-45 mmHg by phentolamine (LP group). Blood chemistry, plasma/interstitial colloid osmotic pressures, plasma volume, fluid balance, fluid extravasation rate and tissue water content were measured or calculated. RESULTS: The plasma volume was significantly lower in the HP group compared with the LP group after 60 minutes of CPB. Net fluid balance was 0.18 (0.05) ml x kg(-1) x min(-1) in the HP group and 0.21 ml x kg(-1) x min(-1) in the LP group (P > 0.05) while fluid extravasation rate was 1.18 (0.5) and 1.13 (0.4) ml x kg(-1) x min(-1) in the HP group and the LP group during CPB (P > 0.05). CONCLUSION: Net fluid balance and fluid extravasation rate were similar in the animals with elevated and with lowered MAP during CPB.

Mean arterial pressure about 40 mmHg during CPB is associated with cerebral ischemia in piglets.

OBJECTIVE: To investigate if a mean arterial pressure below 50 mmHg during CPB may lead to cerebral ischemia. MATERIAL AND METHODS: Piglets with low mean arterial pressure by nitroprusside (LP-group) (n=6) were compared with piglets given norepinephrine to obtain high pressure (HP-group) (n=6) during normothermic and hypothermic CPB. Intracranial pressure, flow and markers of cerebral energy metabolism (microdialysis) were recorded. RESULTS: Mean arterial pressure differed significantly between the groups and stabilized about 40-45 mmHg in the LP-group. Cerebral perfusion pressure decreased to 21.3 (7.7) mmHg in the LP-group and increased to 51.8 (11.2) mmHg in the HP-group at 150 min of CPB (P<0.001, between groups). During bypass the intracerebral glucose concentration decreased significantly in the LP-group. In this group the lactate/pyruvate ratio increased from 15.5 (5.3) to 64.5 (87.6) at 90 min and 45.0 (36.5) at 150 min (P<0.05) with no such changes in the HP-group. Similarly the cerebral glycerol concentration increased significantly in the LP-group, whereas glycerol remained stable in the HP-group. CONCLUSION: Mean arterial pressure about 40 mmHg during CPB is associated with cerebral ischemia.

Cold-induced fluid extravasation during cardiopulmonary bypass in piglets can be counteracted by use of iso-oncotic prime.

OBJECTIVE: Hypothermic cardiopulmonary bypass is associated with increased fluid extravasation. This study aimed to compare whether iso-oncotic priming solutions, in contrast to crystalloids, could reduce the cold-induced fluid extravasation during cardiopulmonary bypass in piglets. METHODS: Three groups were studied: the control group (CT group; n = 10), the albumin group (Alb group; n = 7), and the hydroxyethyl starch group (HES group; n = 7). Prime (1000 mL) and supplemental fluid were acetated Ringer solution, 4% albumin, and 6% hydroxyethyl starch, respectively. After 1 hour of normothermic cardiopulmonary bypass, hypothermic cardiopulmonary bypass (cooling to 28 degrees C within 15 minutes) was initiated and continued to 90 minutes. Fluid needs, plasma volume, changes in colloid osmotic pressure in plasma and interstitial fluid, hematocrit levels, and tissue water content were recorded, and protein masses and fluid extravasation rates were calculated. RESULTS: Colloid osmotic pressure in plasma decreased immediately after the start of cardiopulmonary bypass in the CT group but remained stable in the Alb and HES groups. Colloid osmotic pressure in interstitial fluid tended to decrease in the CT group and remained unchanged in the Alb group, whereas a slight increase was observed in the HES group. Immediately after the start of cooling, fluid extravasation rates increased from 0.15 +/- 0.10 to 0.64 +/- 0.12 mL . kg -1 . min -1 in the CT group, whereas no such increase was observed in the Alb and HES groups. The changes in fluid extravasation rates were reflected by corresponding changes in tissue water content. CONCLUSION: The use of albumin or hydroxyethyl starch as prime to preserve the colloid osmotic pressure during cardiopulmonary bypass causes a reduction in the cold-induced fluid extravasation compared with that seen with crystalloids. Albumin seems more effective than hydroxyethyl starch to limit cold-induced fluid shifts during cardiopulmonary bypass.

Time course variations of haemodynamics, plasma volume and microvascular fluid exchange following surface cooling: an experimental approach to accidental hypothermia.

OBJECTIVE: To describe how surface cooling influences fluid distribution, vascular capacity and haemodynamic variables. METHODS: Seven anaesthetised pigs, following normothermic stabilization for 60 min, were cooled to 27.8+/-1.6 degrees C. Fluid balance, haemodynamics, colloid osmotic pressures (plasma/interstitial fluid), haematocrit [s-albumin/protein] were recorded and plasma volume measured together with tissue perfusion during normothermia, cooling and stable hypothermia (coloured microspheres). Fluid shifts and changes in albumin and protein masses were calculated. At the end tissue water content was assessed. RESULTS: Haemodynamic variables changed with the start of cooling in parallel with a decreasing cardiac output. During hypothermia the haematocrit increased from 0.31+/-0.01 to 0.35+/-0.01 (P < 0.01). Plasma volume decreased from 1139.0+/-65.4 ml at start of cooling to 882.0+/-67.5 ml 3 h later (P < 0.05). In parallel the plasma albumin and protein masses decreased from 37.8+/-2.5 g and 54.6+/-4.0 g to 28.0+/-2.7 g (P < 0.05) and 41.2+/-4.1 g (P > 0.05), respectively. The main changes occurred 120-180 min after start of each experiment. In this period the fluid extravasation rate was elevated (P < 0.05) without influencing the colloid osmotic pressure of plasma/interstitial fluid. The increased fluid filtration was reflected by an increase in tissue water content. CONCLUSION: Our results are in favour of a shift of plasma from circulation to the interstitial space during surface cooling. This conclusion is based on the parallel losses of fluid and proteins from circulation with unchanged colloid osmotic pressures (plasma/interstitial fluid). Inflammation may be involved.