Platelet Function is Preserved After Moderate Cardiopulmonary Bypass Times But Transiently Impaired After Protamine.

OBJECTIVES: Previous studies have described impaired platelet function after cardiopulmonary bypass (CPB). Whether this is still valid in contemporary cardiac surgery is unclear. This study aimed to quantify changes in function and number of platelets during CPB in a present-day cardiac surgery cohort. DESIGN: Prospective, controlled clinical study. SETTING: A single-center university hospital. PARTICIPANTS: Thirty-nine patients scheduled for coronary artery bypass graft surgery with CPB. INTERVENTIONS: Platelet function and numbers were measured at 6 timepoints in 39 patients during and after coronary artery bypass graft surgery; at baseline before anesthesia, at the end of CPB, after protamine administration, at intensive care unit (ICU) arrival, 3 hours after ICU arrival, and on the morning after surgery. MEASUREMENTS AND MAIN RESULTS: Platelet function was assessed with impedance aggregometry and flow cytometry. Platelet numbers are expressed as actual concentration and as numbers corrected for dilution using hemoglobin as a reference marker. There was no consistent impairment of platelet function during CPB with either impedance aggregometry or flow cytometry. After protamine administration, a decrease in platelet function was seen with impedance aggregometry and for some markers of activation with flow cytometry. Platelet function was restored 3 hours after arrival in the ICU. During CPB (85.0 ± 21 min), the number of circulating platelets corrected for dilution increased from 1.73 ± 0.42 × 109/g to 1.91 ± 0.51 × 109/g (p < 0.001). CONCLUSIONS: During cardiac surgery with moderate CPB times, platelet function was not impaired, and no consumption of circulating platelets could be detected. Administration of protamine transiently affected platelet function.

Quantification of platelet function - a comparative study of venous and arterial blood using a novel flow cytometry protocol.

Studies of platelet function in surgical patients often involve both arterial and venous sampling. Possible effects of different sampling sites could be important, but have not been thoroughly investigated. We aimed to compare platelet function in arterial and venous blood samples using a novel flow cytometry protocol and impedance aggregometry. Arterial and venous blood was collected before anesthesia in 10 patients undergoing cardiac surgery of which nine was treated with acetylsalicylic acid until the day before surgery. Flow cytometry included simultaneous analysis of phosphatidylserine exposure, active conformation of the fibrinogen receptor (PAC-1 binding), α-granule and lysosomal release (P-selectin and LAMP-1 exposure) and mitochondrial membrane integrity. Platelets were activated with ADP or peptides activating thrombin receptors (PAR1-AP/PAR4-AP) or collagen receptor GPVI (CRP-XL). Leukocyte-platelet conjugates and P-selectin exposure were evaluated immediately in fixated samples. For impedance aggregometry (Multiplate®), ADP, arachidonic acid, collagen and PAR1-AP (TRAP) were used as activators. Using impedance aggregometry and in 27 out of 37 parameters studied with flow cytometry there was no significant difference between venous and arterial blood sampling. Arterial blood showed more PAC-1 positive platelets when activated with PAR1-AP or PAR4-AP and venous blood showed more monocyte-platelet and neutrophil-platelet conjugates and higher phosphatidylserine exposure with CRP-XL alone and combined with PAR1-AP or PAR4-AP. We found no differences using impedance aggregometry. In conclusion, testing of platelet function by flow cytometry and impedance aggregometry gave comparable results for most of the studied parameters in venous and arterial samples. Flow cytometry identified differences in PAC-1 binding when activated with PAR1-AP, exposure of phosphatidyl serine and monocyte/neutrophil-platelet conjugates, which might reflect differences in blood sampling technique or in flow conditions in this patient cohort with coronary artery disease. These differences might be considered when comparing data from different sample sites, but caution should be exercised if a different protocol is used or another patient group is studied.

Obstructive sleep apnea in Norwegian adults with achondroplasia: a population-based study.

BACKGROUND: Previous studies have found a high prevalence of obstructive sleep apnea (OSA) in children with achondroplasia, but clinical studies on this complication in adults with achondroplasia are lacking. OBJECTIVES: This population-based, cross-sectional study investigated the prevalence, severity, and predictive factors of OSA in Norwegian adults with achondroplasia. METHODS: We collected clinical data on 49 participants. Participants without a preexisting diagnosis of OSA had an overnight sleep registration. OSA was defined as an apnea-hypopnea index (AHI) ≥ 5 plus characteristic clinical symptoms, or AHI ≥ 15. We used the Berlin Questionnaire to assess clinical symptoms of OSA. RESULTS: OSA was found in 59% (29/49) of the participants (95% confidence interval 44 to 73%), of whom 59% (17/29) had moderate to severe OSA (AHI ≥ 15), and 48% (14/29) were previously undiagnosed. Variables predictive of OSA were: excessive daytime sleepiness; unrested sleep; loud snoring; observed nocturnal breathing stops; hypertension; age > 40 years; and BMI > 30 kg/m2. CONCLUSION: OSA was highly prevalent in Norwegian adults with achondroplasia, which we believe is representative of this population worldwide. Follow-up of adults with achondroplasia should include assessment of symptoms and signs of OSA, with a low threshold for conducting an overnight sleep registration if findings suggestive of OSA are present.

Protamine stimulates platelet aggregation in vitro with activation of the fibrinogen receptor and alpha-granule release, but impairs secondary activation via ADP and thrombin receptors.

Heparin and protamine are fundamental in the management of anticoagulation during cardiac surgery. Excess protamine has been associated with increased bleeding. Interaction between protamine and platelet function has been demonstrated but the mechanism remains unclear. We examined the effect of protamine on platelet function in vitro using impedance aggregometry, flow cytometry, and thrombin generation. Platelets were exposed to protamine at final concentrations of 0, 20, 40, and 80 µg/mL, alone or together with adenosine diphosphate (ADP) or thrombin PAR1 receptor-activating peptide (TRAP). We found that in the absence of other activators, protamine (80 µg/mL) increased the proportion of platelets with active fibrinogen receptor (binding of PAC-1) from 3.6% to 97.0% (p < .001) measured with flow cytometry. Impedance aggregometry also increased slightly after exposure to protamine alone. When activated with ADP or TRAP protamine at 80 µg/mL reduced aggregation, from 73.8 ± 29.4 U to 46.9 ± 21.1 U (p < .001) with ADP and from 126.4 ± 16.1 U to 94.9 ± 23.7 U (p < .01) with TRAP. P-selectin exposure (a marker of alpha-granule release) measured by median fluorescence intensity (MFI) increased dose dependently with protamine alone, from 0.76 ± 0.20 (0 µg/mL) to 10.2 ± 3.1 (80 µg/mL), p < .001. Protamine 80 µg/mL by itself resulted in higher MFI (10.16 ± 3.09) than activation with ADP (2.2 ± 0.7, p < .001) or TRAP (5.7 ± 2.6, p < .01) without protamine. When protamine was combined with ADP or TRAP, there was a concentration-dependent increase in the alpha-granule release. In conclusion, protamine interacts with platelets in vitro having both a direct activating effect and impairment of secondary activation of aggregation by other agonists.

Cost analysis comparison between peripherally inserted central catheters and implanted chest ports in patients with cancer-A health economic evaluation of the PICCPORT trial.

BACKGROUND: A reliable central venous access device is a cornerstone in the treatment of cancer. Both peripherally inserted central catheters (PICC) and totally implanted chest ports (PORT) are commonly used for the delivery of chemotherapy. Both types of catheter can cause adverse events such as catheter-related deep venous thrombosis (CR-DVT), infection and mechanical complications. METHOD: We conducted a randomized controlled trial including 399 patients with cancer and performed a health economic evaluation investigating the cost related to PICCs and PORTs using several clinically relevant dimensions from a healthcare perspective. The cost was determined using process and cost estimate models. RESULT: PICCs are associated with a higher total cost when compared with PORTs. Combining the costs of all categories, the prize per inserted device was 824.58 EUR for PICC and 662.34 EUR for PORT. When adjusting for total catheter dwell time the price was 6.58 EUR/day for PICC and 3.01 EUR/day for PORT. The difference in CR-DVT was the main contributor to the difference in cost. The daily cost of PICC is approximately twice to that of PORT. CONCLUSION: We have demonstrated that the cost from a healthcare perspective is higher in cancer patients receiving a PICC than to those with a PORT. The difference is driven mainly by the cost related to the management of adverse events. Our findings are relevant to anaesthetists, oncologists and vascular access clinicians and should be considered when choosing vascular access device prior to chemotherapy.

Clinical impact of peripherally inserted central catheters vs implanted port catheters in patients with cancer: an open-label, randomised, two-centre trial.

BACKGROUND: Centrally inserted totally implanted vascular access ports (PORTs) and peripherally inserted central catheters (PICCs) are widely used for the administration of chemotherapy. Our aim was to study the incidence of catheter-related deep venous thrombosis in patients with cancer receiving chemotherapy through either a PICC or a PORT. METHODS: Adults with non-haematological cancer (mainly breast and colorectal) from two Swedish oncology centres were included and followed for up to 1 yr. Patients were randomly assigned to receive a single-lumen PICC or PORT. The primary end point was the occurrence of a clinically significant catheter-related deep venous thrombosis, and the secondary end point was a composite of adverse events related to the catheter: insertion complication, thrombosis, occlusion, infection, and mechanical problems. RESULTS: The trial recruited 399 participants (PICC, n=201; PORT, n=198) between March 2013 and February 2017. The PICCs were associated with 16 (8%) deep venous thromboses compared with two (1%) in the PORT group (HR=10.2; 95% confidence interval, 2.3-44.6; P=0.002). The overall incidence of composite adverse events was higher for patients with a PICC compared with those with a PORT (HR=2.7; 95% confidence interval, 1.6-4.6; P<0.001). CONCLUSIONS: PICCs are associated with higher risk for catheter-related deep venous thrombosis and other adverse events when compared with PORTs. This increased risk should be considered when choosing a vascular access device for chemotherapy, especially in patients with solid malignancy. CLINICAL TRIAL REGISTRATION: NCT01971021.

Better platelet function, less fibrinolysis and less hemolysis in re-transfused residual pump blood with the Ringer's chase technique - a randomized pilot study.

INTRODUCTION: Residual pump blood from the cardiopulmonary bypass (CPB) circuit is often collected into an infusion bag (IB) and re-transfused. An alternative is to chase the residual blood into the circulation through the arterial cannula with Ringer's acetate. Our aim was to assess possible differences in hemostatic blood quality between these two techniques. METHODS: Forty adult patients undergoing elective coronary artery bypass graft surgery with CPB were randomized to receive the residual pump blood by either an IB or through the Ringer's chase (RC) technique. Platelet activation and function (impedance aggregometry), coagulation and hemolysis variables were assessed in the re-transfused blood and in the patients before, during and after surgery. Results are presented as median (25-75 quartiles). RESULTS: Total hemoglobin and platelet levels in the re-transfused blood were comparable with the two methods, as were soluble platelet activation markers P-selectin and soluble glycoprotein VI (GPVI). Platelet aggregation (U) in the IB blood was significantly lower compared to the RC blood, with the agonists adenosine diphosphate (ADP) 24 (10-32) vs 46 (33-65), p<0.01, thrombin receptor activating peptide (TRAP) 50 (29-73) vs 69 (51-92), p=0.04 and collagen 24 (17-28) vs 34 (26-59), p<0.01. The IB blood had higher amounts of free hemoglobin (mg/L) (1086 (891-1717) vs 591(517-646), p<0.01) and D-dimer 0.60 (0.33-0.98) vs 0.3 (0.3-0.48), p<0.01. Other coagulation variables showed no difference between the groups. CONCLUSIONS: The handling of blood after CPB increases hemolysis, impairs platelet function and activates coagulation and fibrinolysis. The RC technique preserved the blood better than the commonly used IB technique.

Definition of nocturnal gastroesophageal reflux for studies on respiratory diseases.

OBJECTIVE: Nocturnal gastroesophageal reflux (nGER) has been associated with respiratory diseases. Our aim was to study a questionnaire method to identify nGER subjects with respiratory involvement in a general population. MATERIAL AND METHODS: A subgroup of Icelandic participants in the European Community Respiratory Health Survey III (ECRHS III) reporting symptoms of nGER (n = 48) as well as age and gender paired controls (n = 42) were studied further by a structured interview, questionnaires, laryngeal fibrescopy, and exhaled breath condensate. A subgroup underwent 24-h oesophageal pH impedance (24-h MII-pH) measurements. Symptoms of nGER were assessed with a modified version of the reflux disease questionnaire (RDQ), where symptoms were divided into daytime and nocturnal. A report of nGER both at baseline and at follow-up was defined as persistent nGER. RESULTS: Participants reporting persistent nGER had significantly more signs of laryngopharyngeal reflux according to the reflux finding score than those without nGER (Mean ± SD: 5.1 ± 2.3 vs. 3.9 ± 2.2, p = 0.02). Of the 16 persistent nGER subjects that underwent 24-h MII-pH, 11 had abnormal gastroesophageal reflux, but none of three control subjects (69% vs. 0%). Pepsin was more commonly found in exhaled breath condensate in the nGER group (67% vs. 45%, p = 0.04). CONCLUSIONS: Participants with nGER symptoms at least once a month, reported on two occasions, had a high level of positive 24-h MII-pH measurements, laryngeal inflammation and pepsin in exhaled breath condensate. This nGER definition identified a representable group for studies on nGER and respiratory diseases in a general population.

Protamine reduces whole blood platelet aggregation after cardiopulmonary bypass.

OBJECTIVES: Platelet dysfunction is an important cause of postoperative bleeding after cardiac surgery. Protamine is routinely used for reversal of heparin after cardiopulmonary bypass (CBP), but may affect platelet aggregation. We assessed changes in platelet function in relation to protamine administration. DESIGN: Platelet aggregation was analyzed by impedance aggregometry before and after protamine administration in 25 adult cardiac surgery patients. Aggregation was also studied after in vitro addition of heparin and protamine. The activators adenosine diphosphate (ADP), thrombin receptor activating peptide-6 (TRAP), arachidonic acid (AA) and collagen (COL) were used. RESULTS: Platelet aggregation was reduced by approximately 50% after in vivo protamine administration; ADP 640 ± 230 (AU*min, mean ± SD) to 250 ± 160, TRAP 939 ± 293 to 472 ± 260, AA 307 ± 238 to 159 ± 143 and COL 1022 ± 350 to 506 ± 238 (all p < 0.001). Aggregation was also reduced after in vitro addition of protamine alone with activators ADP from 518 ± 173 to 384 ± 157 AU*min p < 0.001, and AA 449 ± 311 to 340 ± 285 (p < 0.01) and protamine combined with heparin (1:1 ratio) with activators ADP to 349 ± 160 and AA to 308 ± 260 (both p < 0.001); and COL from 586 ± 180 to 455 ± 172 (p < 0.05). CONCLUSIONS: Protamine given after CPB markedly reduces platelet aggregation. Protamine added in vitro also reduces platelet aggregation, by itself or in combination with heparin.

Psychoeducational support to post cardiac surgery heart failure patients and their partners--a randomised pilot study.

OBJECTIVES: Postoperative heart failure is a serious complication that changes the lives of both the person who is critically ill and family in many ways. The purpose of this study was to evaluate the effects of an intervention in postoperative heart failure patient-partner dyads regarding health, symptoms of depression and perceived control. RESEARCH METHODOLOGY/DESIGN: Pilot study with a randomised controlled design evaluating psychosocial support and education from an interdisciplinary team. SETTING: Patients with postoperative heart failure and their partners. MAIN OUTCOME MEASURES: SF-36, Beck Depression Inventory, Perceived Control at baseline, 3 and 12 months. RESULTS: A total of 42 patient-partner completed baseline assessment. Partners in the intervention group increased health in the role emotional and mental health dimensions and patients increased health in vitality, social function and mental health dimensions compared with the control group. Patients' perceived control improved significantly in the intervention group over time. CONCLUSION: Psychoeducational support to post cardiac surgery heart failure dyads improved health in both patients and partners at short term follow-up and improved patients' perceived control at both short and long-term follow-up. Psychoeducational support appears to be a promising intervention but the results need to be confirmed in larger studies.

A prospective observational study on 249 subcutaneous central vein access ports in a Swedish county hospital.

BACKGROUND: Reliable central vein access is a fundamental issue in modern advanced oncological care. The aim of this study was to determine the incidence of complications and patient perception regarding central vein access ports. METHODS: We prospectively studied 249 single lumen access ports implanted between 1 July 2008 and 15 March 2010 in a mixed patient population at a 500-bed secondary level hospital in Sweden. We determined the number of catheter days, infection rate and mechanical complications, as well as patient satisfaction regarding the access port, over a six-month follow-up period. RESULTS: Two hundred and forty-four different patients received 249 ports yielding a total of 37 763 catheter days. Ultrasound and fluoroscopic guidance was used in 98% of procedures. Vein access was obtained percutanously by an anaesthesiologist in all cases. There was no case of pneumo- or haemothorax. The incidence of catheter-related bloodstream infection, was 0.05/1000 catheter days and the incidence of pocket/tunnel infection was 0.39/1000 catheter days. Clinically apparent deep vein thrombosis occurred in four patients (1.6%). Patient satisfaction was overall high. CONCLUSION: These results confirm that our team-based approach with written easily accessible evidence-based guidelines and a structured education programme leads to a very low complication rate and a high degree of patient satisfaction.

Real-time intraoperative visualization of myocardial circulation using augmented reality temperature display.

For direct visualization of myocardial ischemia during cardiac surgery, we tested the feasibility of presenting infrared (IR) tissue temperature maps in situ during surgery. A new augmented reality (AR) system, consisting of an IR camera and an integrated projector having identical optical axes, was used, with a high resolution IR camera as control. The hearts of five pigs were exposed and an elastic band placed around the middle of the left anterior descending coronary artery to induce ischemia. A proximally placed ultrasound Doppler probe confirmed reduction of flow. Two periods of complete ischemia and reperfusion were studied in each heart. There was a significant decrease in IR-measured temperature distal to the occlusion, with subsequent return to baseline temperatures after reperfusion (baseline 36.9 ± 0.60 (mean ± SD) versus ischemia 34.1 ± 1.66 versus reperfusion 37.4 ± 0.48; p < 0.001), with no differences occurring in the non-occluded area. The AR presentation was clear and dynamic without delay, visualizing the temperature changes produced by manipulation of the coronary blood flow, and showed concentrically arranged penumbra zones during ischemia. Surface myocardial temperature changes could be assessed quantitatively and visualized in situ during ischemia and subsequent reperfusion. This method shows potential as a rapid and simple way of following myocardial perfusion during cardiac surgery. The dynamics in the penumbra zone could potentially be used for visualizing the effect of therapy on intraoperative ischemia during cardiac surgery.

Long-term follow-up of patients operated with Uvulopalatopharyngoplasty from 1985 to 1991.

OBJECTIVES: Short-term outcome and side effects after Uvulopalatopharyngoplasty (UPPP) are well recognized. However, there is a lack of knowledge of the long-term outcome and side effects after this surgery. This study was completed to investigate the outcome and side effects 20 years after UPPP for snoring and obstructive sleep apnoea. METHODS: Medical records of patients who underwent UPPP surgery for sleep apnoea and snoring between 1985 and 1991 were investigated retrospectively. A specific questionnaire focusing on the present health profile, side effects of previous UPPP surgery and present sleeping patterns of patients was mailed out. RESULTS: UPPP patients, 186 (including 11 females) were identified. Of these, 35 (19%) had passed away and 7 (4%) were not located. 129 patients (mean: age 68 years, range 43-83) of the possible 144 patients answered the questionnaire (response rate 90%). At follow-up, 41 patients (32%) used continuous positive airway pressure (CPAP). 66 of the patients (52%) were satisfied with the result of the operation, but 61 (47%) were not satisfied. 49 patients (38%) reported persistent side effects (problems with nasal regurgitation 18 (14%), swallowing 26 (20%), changed voice 15 (12%), and pain in the oral cavity 15 (12%). CONCLUSION: Almost 50% of patients operated with UPPP were not satisfied with the result of the operation after about 20 years, and one third used CPAP at follow-up. A large proportion of patients still experienced side effects, which, after this time, are likely to be permanent.

Addressing spouses' unique needs after cardiac surgery when recovery is complicated by heart failure.

BACKGROUND: Cardiac surgery places extensive stress on spouses who often are more worried than the patients themselves. Spouses can experience difficult and demanding situations when the partner becomes critically ill. OBJECTIVES: To identify, describe, and conceptualize the individual needs of spouses of patients with complications of heart failure after cardiac surgery. METHODS: Grounded theory using a mix of systematic coding, data analysis, and theoretical sampling was performed. Spouses, 10 women and 3 men between 39 and 85 years, were interviewed. RESULTS: During analysis, the core category of confirmation was identified as describing the individual needs of the spouses. The core category theoretically binds together three underlying subcategories: security, rest for mind and body, and inner strength. Confirmation facilitated acceptance and improvement of mental and physical health among spouses. CONCLUSIONS: By identifying spouses' needs for security, rest for mind and body, and inner strength, health care professionals can confirm these needs throughout the caring process, from the critical care period and throughout rehabilitation at home. Interventions to confirm spouses' needs are important because they are vital to the patients' recovery.

Proinflammatory cytokines increase the rate of glycolysis and adenosine-5'-triphosphate turnover in cultured rat enterocytes.

OBJECTIVE: Measurements of steady-state adenosine-5'-triphosphate (ATP) levels in tissue samples from patients or experimental animals with sepsis or endotoxemia provide little information about the rate of ATP production and consumption in these conditions. Accordingly, we sought to use an in vitro "reductionist" model of sepsis to test the hypothesis that proinflammatory cytokines modulate ATP turnover rate. DESIGN: In vitro "reductionist" model of sepsis. SETTING: University laboratory. SUBJECTS: Cultured rat enterocyte-like cells. INTERVENTIONS: IEC-6 nontransformed rat enterocytes were studied under control conditions or following incubation for 24 or 48 hrs with cytomix, a mixture of tumor necrosis factor-alpha (10 ng/mL), interleukin-1beta (1 ng/mL), and interferon-gamma (1000 units/mL). To measure ATP turnover rate, ATP synthesis was acutely blocked by adding to the cells a mixture of 2-deoxyglucose (10 mM), potassium cyanide (8 mM), and antimycin A (1 microM). ATP content was measured at baseline (before metabolic inhibition) and 0.5, 1, 2, 5, and 10 mins later. Log-linear ATP decay curves were generated and the kinetics of ATP utilization thereby calculated. MEASUREMENTS AND MAIN RESULTS: ATP consumption rate was higher in cytomix-stimulated compared with control cells (3.11 +/- 1.39 vs. 1.25 +/- 0.66 nmol/min, respectively; p <.01). Similarly, the half-time for ATP disappearance was shorter in cytomix-stimulated compared with control cells (2.63 +/- 1.00 vs. 6.21 +/- 3.49; p <.05). In contrast to these findings, the rate of ATP disappearance was similar in cytokine-naïve and immunostimulated IEC-6 cells when protein and nucleic acid synthesis were inhibited by adding 50 microg/mL cycloheximide and 5 microg/mL actinomycin D to cultures for 4 hrs. The rates of glucose consumption and lactate production were significantly greater in cytomix-stimulated compared with controls cells. CONCLUSIONS: Incubation of IEC-6 cells with cytomix significantly increased ATP turnover. Increased ATP turnover rate was supported by increases in the rate of anaerobic glycolysis. These findings support the view that proinflammatory mediators impose a metabolic demand on visceral cells. In sepsis, cells may be more susceptible to dysfunction on the basis of diminished oxygen delivery and/or mitochondrial dysfunction.