The role of computer-assisted cryotherapy in the postoperative treatment after total knee arthroplasty: positive effects on pain and opioid consumption.

PURPOSE: The aim of this study was to investigate whether computer-assisted cryotherapy is effective in reducing postoperative pain and analgesics consumption, next to improving functional outcome and patient satisfaction after total knee arthroplasty (TKA). The hypothesis is that computer-assisted cryotherapy has positive effects on postoperative pain after TKA. METHODS: A single-centre non-blinded randomised controlled trial was designed to study the early (first postoperative week) and late (2 and 6 weeks postoperatively) additive effect of computer-assisted cooling after TKA. Participants scheduled for a TKA were randomly allocated to a cold (cryotherapy) C-group or a regular (control) R-group. Next to usual postoperative care for both groups, the C-group received computer-assisted cryotherapy during the first seven postoperative days. Primary outcome was pain, monitored with the numerical rating scale for pain and use of opioid escape medication. Secondary outcomes were function and swelling, monitored by active range of motion, timed up and go test and circumference measurements; patient-reported outcome measurements (KOOS and WORQ questionnaires); and patient satisfaction, monitored by the numerical rating scale for satisfaction. RESULTS: 102 patients participated in this study, both groups contained 51 patients. On most days during the first week, patients in the C-group scored significantly lower NRS pain scores and registered significantly less use of opioid escape medication. In a sub-analysis of 57 patients using the same standard pain protocol, patients in the C-group (n = 28) used less oxycodone during the first postoperative week. There were no significant differences between both groups in active range of motion, timed up and go, or circumference measurements. For the WORQ questionnaire, there was a significant difference between the two groups 6 weeks postoperatively in favour of the C-group. This could be however due to a reduced validity of this questionnaire shortly after TKA. The satisfaction score was not significantly different between both groups. CONCLUSION: Computer-assisted cryotherapy following TKA can be beneficial during the first postoperative week in terms of pain reduction and diminished opioid consumption. No clear differences in knee function or swelling were seen. LEVEL OF EVIDENCE: Therapeutic study with level of evidence I.

Accelerometer Measured Sedentary and Physical Activity Behaviors of Working Patients after Total Knee Arthroplasty, and their Compensation Between Occupational and Leisure Time.

Purpose Objective measurements of sedentary and physical activity (PA) behavior are scarce among working-age patients who undergo total knee arthroplasty (TKA). Aim was to assess sedentary and PA behaviors using accelerometers and to identify compensation effects between occupational and leisure time of sedentary and PA behavior. Methods One year post-TKA, 51 patients wore an ActiGraph(GT3x) accelerometer for 7 days. Sedentary time, prolonged sedentary bouts (≥ 30 min) and PA (light-intensity and moderate-to-vigorous PA) were examined. Compliance with the guideline of > 150 min moderate-to-vigorous PA per week was calculated. Compensation effects were analyzed using multilevel models, splitting effects into routine and within-day compensation, stratifying by physical and non-physical jobs. The routine compensation effects are the ones of interest, representing habitual compensation during a week. Results Participants spent 60% of time in sedentary bouts and 17% in prolonged sedentary bouts, with 37% of PA spent in light-intensity and 3% in moderate-to-vigorous activity. About 70% of patients met the PA guideline. Routine compensation effects were found for workers in physical jobs, who compensated for their occupational light-intensity PA with less light-intensity PA during leisure time. Workers in non-physical jobs did not compensate for their occupational prolonged sedentary bouts, as these continued during leisure time. Conclusion This study showed that working TKA patients are highly sedentary 1 year after surgery, but most met the PA guideline. Especially those with non-physical jobs do not compensate for their occupational prolonged sedentary bouts. This stresses the need to stimulate PA among TKA patients not complying with the guidelines and those with non-physical jobs.

Leucocyte filtration of residual heart-lung machine blood in children undergoing congenital heart surgery.

Cardiopulmonary bypass (CPB) leads to a generalized inflammatory reaction, resulting in increased postoperative leucocyte counts and decreased pulmonary function. In adults, removal of leucocytes from the residual heart-lung machine blood after CPB improved postoperative oxygenation. In children, however, the clinical effects of leucocyte filtration of the residual heart-lung machine blood are unknown. Therefore, we measured postoperative leucocyte counts and arterial blood oxygenation in children undergoing congenital cardiac surgery in a randomized prospective study. Anaesthesia and CPB were standardized. After CPB, the residual heart-lung machine blood was collected as usual. In a group of 25 children, this blood was filtered with a leucocyte depletion filter before transfusion. A control group of 25 children received this blood unfiltered. We found that the postoperative leucocyte counts were significantly lower in the filter group than in the control group (p = 0.02, repeated measurements ANOVA). This difference reached a maximum on the second postoperative day (12.9 x 10(9)/L filter versus 15.9 x 10(9)/L control, p = 0.02, Student's t-test). Values for the arterial blood oxygenation on the first postoperative day were not different between the two groups (15.5 +/- 1 kPa filter versus 14.6 +/- 1.3 kPa control, p = 0.57, Student's t-test). We conclude that leucocyte filtration of the residual heart-lung machine blood reduced systemic leucocyte counts, but did not improve arterial blood oxygenation in children after congenital heart surgery.

The rationale for fat filtration during cardiac surgery.

Improved filter technology may enable the removal of specific substances such as lipids from the blood. Lipids form a heterogeneous group of compounds, but during surgery, the main interest is focussed on triglycerides, glycerol and free fatty acids. Fat emboli have been demonstrated in the brain after cardiac surgery and are associated with ischaemic brain injury. Fat emboli have also been demonstrated in lung and kidney tissue. Lung tissue and leucocytes are especially vulnerable to the effects of free fatty acids. The surgical wound suction blood during cardiac surgery contains a considerable quantity of microemboli. Therefore, as a first step to determining the place of fat filtration during cardiac surgery, the use of a fat removal filter for surgical wound suction blood is advocated.

Effects of preoperative treatment with diltiazem on diastolic ventricular function after coronary artery bypass graft surgery.

OBJECTIVE: To examine whether preoperative treatment with diltiazem could ameliorate left ventricular (LV) diastolic dysfunction in patients after coronary artery bypass graft (CABG) surgery. DESIGN: Prospective, nonrandomized clinical study. SETTING: University hospital. PARTICIPANTS: Thirty-four patients with preserved LV function undergoing elective CABG surgery. INTERVENTIONS: According to medical history, patients were divided into 2 groups: patients not receiving diltiazem (n = 17) and patients treated with once-daily oral diltiazem for at least 2 weeks (n = 17). All patients received preoperative beta-blockers. MEASUREMENTS AND MAIN RESULTS: After induction of anesthesia, after sternal closure, and 4 hours after cardiopulmonary bypass (CPB), mitral and pulmonary venous flow velocities were measured with pulsed Doppler. LV short-axis end-diastolic area by Doppler transesophageal echocardiography (TEE) and hemodynamic variables were obtained simultaneously at comparable pulmonary capillary wedge pressures. Postoperatively, increased peak E and A velocities were observed in patients with diltiazem and controls and returned to baseline 4 hours post-CPB in controls. Changes in these velocities did not result in a decreased E/A ratio. Peak A velocity, E/A ratio, and E wave deceleration time were significantly dependent on heart rate, not peak E velocity. End-diastolic area at comparable pulmonary capillary wedge pressure remained unchanged. In relation to diltiazem, only peak A velocity and time velocity integral of the A wave (TVI-A) at 4 hours post-CPB differed from controls. CONCLUSION: Diastolic function is preserved after CABG surgery and is not altered by diltiazem in patients with preserved LV systolic function. The persistence of increased peak A velocity and TVI-A into the postoperative period suggests improved atrial systolic function with diltiazem.

Mallory-Weiss tear following cardiac surgery: transoesophageal echoprobe or nasogastric tube?

A case of fatal upper gastrointestinal bleeding from a Mallory-Weiss tear after transoesophageal echocardiography during cardiac surgery is reported. After the echo-cardiographic examination, which is considered a safe procedure, a nasogastric tube was inserted which immediately revealed bright red blood. Eventually the patient lost 9 litres of blood. The role of the echo-probe and the nasogastric tube in causing the Mallory-Weiss tear is discussed. Although this case is not conclusive about the mechanism of oesophageal damage, it is suggested that the safety recommendations for transoesophageal echocardiography also apply for instrumentation of the oesophagus with a nasogastric tube after the transoesophageal echocardiographic examination.

Filtration of activated granulocytes during cardiopulmonary bypass surgery: a morphologic and immunologic study to characterize the trapped leukocytes.

Cardiopulmonary bypass surgery induces an inflammatory reaction among others by activation of granulocytes. Leukocyte filtration has been shown to reduce the postoperative morbidity mediated by activated granulocytes. However, little is known about the mechanism of filter-leukocyte interaction. This study examines whether a leukocyte filter removes activated granulocytes or a general leukocyte population. Eleven patients undergoing cardiopulmonary bypass surgery were included in this study. Leukocyte filtration was achieved before the reperfusion phase with a Pall non-woven polyester filter located at the venous side of the heart-lung machine. After filtration, the trapped granulocytes inside the filter were examined morphologically with light and scanning electron microscopy and immunologically by CD45RO antigen binding to the filter material. Furthermore, leukocyte release markers were measured to determine whether cells were activated during filtration. Microscopic evaluation revealed 84% granulocytes and 14% lymphocytes trapped in the filter, compared with 78% granulocytes and 22% lymphocytes in the blood before filtration. Granulocytes were trapped significantly more in the first blood contact layer of the filter material than in the middle layer and last layer, whereas lymphocytes trapped slightly more in the middle layer. The near maximum level of CD45RO expression was measured on granulocytes trapped inside the filter material, whereas CD2 and CD19 measured on lymphocytes were bound to a minor extent. Beta-glucuronidase concentration did not increase after filtration, suggesting the absence of activation of granulocytes by filtration. A leukocyte filter made of non-woven polyester material removes the activated granulocytes rather than leukocytes at random. This implies that this particular type of leukocyte removal filter is suitable for use in cardiopulmonary bypass patients whose granulocytes in the circulation are activated. Furthermore, measurement of activated granulocytes instead of total leukocyte count is likely preferable for functional assessment of leukocyte removal devices.

Leukocyte depletion during cardiac operation: a new approach through the venous bypass circuit.

BACKGROUND: Leukocyte depletion recently has been introduced for cardiac surgical patients to attenuate leukocyte-mediated inflammation and organ reperfusion injury. We evaluated the feasibility of a new leukocyte depletion method in which systemic leukocyte depletion is achieved through the venous side of the cardiopulmonary bypass circuit under low blood flow. METHODS: Forty cardiac surgical patients undergoing cardiopulmonary bypass were allocated randomly to a leukocyte depletion group (n = 20) and a control group (n = 20). In the depletion group, leukocyte filtration was achieved with two filter sets located between the venous drainage and the venous reservoir. Leukocyte filtration was commenced after the start of rewarming but before the release of the aortic cross-clamp, and it was driven by a spare roller pump of the heart-lung machine. RESULTS: All the episodes of filtration went smoothly within a period of 10 minutes and with a blood flow rate of 400 mL/min. The mean leukocyte removal rate calculated at the end of filtration was 69%. Circulating leukocytes were reduced by 38% in the depletion group compared with the control group at the moment of cross-clamp release (4.3x10(9)/L versus 6.8x10(9)/L, p<0.05). The postoperative inflammatory response also was reduced as indicated by less production of interleukin-8 (p<0.05). Clinically, there was no significant difference between the two groups in postoperative PaO2 or pulmonary hemodynamics. CONCLUSIONS: It is technically feasible to deplete circulating leukocytes through the venous side of the cardiopulmonary bypass circuit with a low blood flow rate. Future studies should focus on the duration and timing of leukocyte depletion to optimize the methodology of leukocyte depletion for cardiac surgical patients.

Efficiency and safety of leukocyte filtration during cardiopulmonary bypass for cardiac surgery.

BACKGROUND: Leukocyte filtration of systemic blood during cardiopulmonary bypass surgery to reduce post-operative morbidity has not yet been established because of the enormous leukocyte release from the third space. This study was designed to examine the efficiency and safety of leukocyte filtration by a new prototype large capacity leukocyte filter. PATIENTS AND METHODS: Patients undergoing cardiopulmonary bypass surgery were prospectively divided into two groups: a leukocyte removal group (n = 11) receiving leukocyte filtration during cardiopulmonary bypass and a control group (n = 20) with no filtration. The filtration efficiency was indicated by electronic leukocyte counts before and after filtration and the clinical efficiency to reduce post-operative morbidity was indicated by PaO2. Safety was indicated by monitoring the filtration pressure and leukocyte release products across the filter, as well as by examining the post-filtration filter by light and electron microscopy. RESULTS: On an average, 75% of all entering leukocytes were removed by the filter. The post-operative PaO2 showed a tendency to improve after filtration. During filtration, the pressure across the filter material increased in five cases, accompanied by an increase in post-filter plasma hemoglobin and beta-glucoronidase. Within these filters accumulations of fibrin network with many trapped leukocytes were discovered microscopically. CONCLUSIONS: The filter was efficient in filtering leukocytes, but the filtration efficiency slowed at the end of filtration. Furthermore, the patients' post-operative parameters showed a tendency to improve after filtration. However, flow obstruction by means of clotting seems to be an important issue of safety involved in the filtration of large numbers of leukocytes for cardiopulmonary surgical patients.

Leukocyte depletion results in improved lung function and reduced inflammatory response after cardiac surgery.

Leukocyte depletion during cardiopulmonary bypass has been demonstrated in animal experiments to improve pulmonary function. Conflicting results have been reported, however, with clinical depletion by arterial line filter of leukocytes at the beginning of cardiopulmonary bypass. In this study, we examined whether leukocyte depletion from the residual heart-lung machine blood at the end of cardiopulmonary bypass would improve lung function and reduce the postoperative inflammatory response. Thirty patients undergoing elective heart operations were randomly allocated to a leukocyte-depletion group or a control group. In the leukocyte-depletion group (n = 20), all residual blood (1.2 to 2.1 L) was filtered by leukocyte-removal filters and reinfused after cardiopulmonary bypass, whereas in the control group an identical amount of residual blood after cardiopulmonary bypass was reinfused without filtration (n = 10). Leukocyte depletion removed more than 97% of leukocytes from the retransfused blood (p < 0.01) and significantly reduced circulating leukocytes (p < 0.05) and granulocytes (p < 0.05) compared with the control group. Levels of the inflammatory mediator thromboxane B2 determined at the end of operation (p < 0.05) were significantly lower in the depletion group than in the control group, whereas no statistical differences in interleukin-6 levels were found between the two groups. After operation, pulmonary gas exchange function (arterial oxygen tension at a fraction of inspired oxygen of 0.4) was significantly higher in the leukocyte-depletion group 1 hour after arrival to the intensive care unit (p < 0.05) and after extubation (p < 0.05). There were no statistical differences between the two groups with respect to postoperative circulating platelet levels and blood loss, and no infections were observed during the whole period of hospitalization. These results suggest that leukocyte depletion of the residual heart-lung machine blood improves postoperative lung gas exchange function and is safe for patients who are expected to have a severe inflammatory response after heart operations.

Quantification of mitoxantrone in bone marrow by high-performance liquid chromatography with electrochemical detection.

An analytical method for the determination of mitoxantrone in bone marrow was developed using high-performance liquid chromatography with electrochemical detection. The extraction procedure was optimized by investigating several factors which potentially could influence the recovery of mitoxantrone from bone marrow cells. The mean recovery of mitoxantrone from rat bone marrow was found to be 81.7% with a coefficient of variation 3.8%. High-performance liquid chromatography was carried out to quantitate mitoxantrone using ametantrone as internal standard. The detection limit of our analytical method amounts to 100 pg on-column, corresponding to 1 ng/ml of cell suspension containing 2 x 10(7) cells and a day-to-day variation of maximally 8%. Storage of bone marrow samples, containing mitoxantrone, for one to fourteen days resulted in a mean recovery of 94%, as compared to freshly analysed samples. Subsequently we studied the pharmacokinetics of mitoxantrone in rat bone marrow. It appeared that after an intravenous bolus injection of mitoxantrone (2.5 mg/kg) in rats, the drug accumulated in the femoral bone marrow for about four days, and thereafter gradually declined.

Lung damage following bone marrow transplantation: II. The contribution of cyclophosphamide.

The effect of high-dose cyclophosphamide (Cy), either alone or in combination with irradiation, upon the development of interstitial pneumonitis (IP) after bone marrow transplantation (BMT) was investigated in a Brown Norway rat model. The parameters that were examined included ventilation rate, mortality, and histopathology. No damage to the lungs was observed in rats given Cy alone in supralethal dosages plus BMT, and mortality resulted from severe aplasia of hemopoietic and lymphoid tissues with multifocal hemorrhages, secondary infections, and sepsis. Two separate periods of mortality were observed within the first 180 days following whole thorax irradiation with a high dose rate (HDR; 0.8 Gy/min) or a low dose rate (LDR; 0.05 Gy/min). The addition of Cy prior to irradiation resulted in an increased mortality in the first period (before day 100) in all experimental groups. The influence of Cy on mortality at 180 days however, was different for the HDR and LDR experiments. The LD50-180 after HDR irradiation, dose range 8 to 18 Gy, was not significantly altered by the addition of Cy (100 mg/kg) 1 day prior to irradiation, whereas Cy (100 mg/kg) 1 day prior to LDR irradiation, dose range: 16 to 24 Gy, caused an enhancement of radiation damage with a decrease of the LD50-180 by 1.33 Gy. The dose modification factor (DMF) was 1.07. This enhancement was no longer significant after splitting up the dose of Cy in two dosages of 50 mg/kg given on 2 consecutive days prior to irradiation with a LDR. The extrapolation of the data in this rat model to available dose-response curves on IP after BMT and radiation pneumonitis in humans, implied that non-infectious IP is a radiation pneumonitis that is only slightly enhanced by Cy.

Late effects of cyclophosphamide and total body irradiation as a conditioning regimen for bone marrow transplantation in rats (a preliminary report).

The longterm survival and occurrence of neoplastic and nonneoplastic lesions following total body irradiation (TBI), 8.5 Gy, with or without additional cyclophosphamide (Cy; 100 mg kg-1 i.p.) treatment as a conditioning regimen for bone marrow transplantation (BMT) were studied in male BN/BiRij rats. The two groups of rats that were treated with Cy (Cy and Cy + TBI) that survived beyond 100 days after treatment, had a severely decreased median (post treatment) survival time (Cy + TBI: 14.5 months and Cy: 14.1 months). Survival time in the TBI group was moderately decreased (18.5 months) as compared with the untreated controls (27.2 months). All treatment modalities were carcinogenic according to the raw data. After Cy-treatment a high incidence of, frequently multiple, malignant nerve-sheath tumours (Cy: 66 per cent, Cy + TBI: 31 per cent, controls: 2 per cent) was observed. TBI induced an increased occurrence of a great variety of tumours, especially mesenchymal tumours. This effect was more pronounced in animals receiving TBI alone as compared to animals receiving the combined treatment of Cy + TBI; an effect that most likely resulted from the longer median survival after TBI. The multi-target effect of TBI was also reflected in the occurrence of nonneoplastic effects in a variety of tissues, including high incidences of biliary cysts in the liver and severe testicular atrophy. The most important Cy-induced nonneoplastic lesion was incisor dysplasia, which resulted in feeding problems that could only be partly overcome by administering powdered food. Early mortality in the Cy-treated groups was associated with emaciation and generalized organ atrophy. A more definitive estimate of the late effects of supralethal chemoradiotherapy as part of a treatment of malignant disease has to await the results of various conditioning regimens for BMT in rats employing the acute BN myelocytic leukaemia (BNML) as a rat model for human acute myelocytic leukaemia (AML).

Monocytes and radiation-induced atheromatosis in rabbits.

Previous experiments have shown that local irradiation of the carotid arteries of hypercholesterolemic rabbits results in the development of atheromatosis in the irradiated areas of the arteries. The process starts with the adherence of monocytes to the endothelial layer, their entrance into the subendothelial space, and their subsequent transformation into lipophages (foam cells). Prevention of this type of plaque formation can be achieved by prednisolone (in a lower concentration than previously used) (Vos et al. 1981) and by VP16-213 (Vepesid). Differential blood cell counts demonstrated that the animals subjected to treatment with prednisolone developed a moderate relative lymphocytopenia, whereas treatment with Vepesid resulted in a severe monocytopenia. Since prednisolone treatment only partially prevented plaque formation, whereas Vepesid seemed to fully inhibit the development of plaques, we conclude that although a role of the lymphocyte in the process of plaque formation cannot be excluded, the monocyte seems to play a crucial role in the pathogenesis of radiation-induced atheromatosis.