In Vitro Comparative Assessment of Mechanical Blood Damage Induced by Different Hemodialysis Treatments.

Gradual deterioration of red blood cells (RBCs) due to mechanical stress (chronic hemolysis) is unavoidable during treatments that involve extracorporeal blood circulation, such as hemodialysis (HD). This effect is generally undetectable and does not generate any acute symptoms, but it leads to an increase in plasma free hemoglobin (fHb). There are no absolute safety levels for fHb increase, indicating the need for an empirical evaluation using comparative testing. The increase in fHb levels was investigated in vitro by applying double-needle double-pump HD (HD-DNDP), a new modality in which arterial and venous pumps both run continuously. fHb was measured during typical and worst-case simulated dialysis treatments (double-needle single-pump HD [HD-DNSP], hemodiafiltration [HDF-DN], single-needle double-pump HD [HD-SNDP], and HD-DNDP) performed in vitro using bovine blood for 4 h. Hemolysis-related indices (fHb%; index of hemolysis, IH; and normalized IH) were calculated and used for comparison. The increase in fHb during either HDF-DN or HD-SNDP with Artis and AK200 dialysis machines was similar, while the fHb at the maximum real blood flow rate (Qbreal ) at the completion of the HD-DNDP treatment on Artis was higher than that for HD-DNSP using a Phoenix dialysis machine (fHb% = 1.24 ± 0.13 and 0.92 ± 0.12 for the Artis machine with HD-DNDP at Qbreal = 450 mL/min and Phoenix with HD-DNSP at Qbreal = 500 mL/min, respectively). However, the fHb levels increased linearly, and no steep changes were observed. The increases observed during HD-DNDP were the same order of magnitude as those for widely used bloodlines and treatment modes for delivering dialysis treatments. The observed results matched literature findings, and thus the measured fHb trends are not predicted to have clinical side effects. HD-DNDP treatment with Artis does not merit any additional concern regarding mechanical stress to RBCs compared with that observed for routinely used dialysis treatments, bloodlines and machines. Although the in vitro measurement of the fHb increase in bovine blood does not allow a prediction of the absolute level of blood mechanical damage or the possible effects in humans, such measurements are valuable for assessing hemolytic harm by performing tests comparing the proposed treatment with existing devices.

Multidisciplinary evaluation for severity of hazards applied to hemodialysis devices: an original risk analysis method.

BACKGROUND AND OBJECTIVES: Risk analysis for medical devices is a crucial process to grant adequate levels of safety. Identification of device exposure-related hazards is one of the main objectives. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Hazard analysis for hemodialysis devices has been performed by a multidisciplinary team involving engineers and clinical experts. A potential harm list was identified from clinical and technical experience, postproduction information, and literature. Various hazardous situations (circumstances when the use of the dialysis device may lead to described harms) were described. Such hazardous situations were correlated to the extent of the deviation of a specific device parameter from expected ranges. The clinical severity that was relevant to any specific harm was categorized for each hazardous situation using a descriptive and numerical scale with five levels (from negligible [i.e., discomfort only] to catastrophic [i.e., potentially lethal]). RESULTS: Harms in which the deviation of a parameter strictly coincides with the clinically measured effect on the patient are defined as "direct." Otherwise, when another clinical parameter must be involved to quantify severity, the related harm is considered "indirect." Two complete examples of multidisciplinary evaluation for severity of hazards (MESH) are given for a direct harm (air embolism) and for an indirect harm (hypothermia). For other harms, the maximum value of severity involved is provided. CONCLUSIONS: MESH represents a possible example of risk management for dialysis equipment in which, although the manufacturer is directly responsible, a multidisciplinary task force may contribute to a better link between engineering and clinical perspectives.

In vitro and in vivo evaluation of an oscillometric device for monitoring blood pressure in dialysis patients.

BACKGROUND: Nowadays, an increasing number of dialysis machines lodge a blood pressure (BP) measuring device, whose accuracy has a clear implication for the patients' clinical management. METHODS: An automated oscillometric sphygmomanometer (HD-BPM by Gambro Dasco) used during haemodialysis was submitted to both in vitro and in vivo tests, in order to evaluate some modifications aimed at improving measurement accuracy and consistency. The results were compared with those obtained by another oscillometric monitor (BX-100 by Colin). Three steps of evaluation were followed. First, the maintenance of the overall accuracy requirements prescribed by ANSI/AAMI SP-10 standard was verified. Then, an in vitro validation was carried out by using a test simulator. Finally, during a multi-centre field trial, 392 BP measurement sessions on 53 dialysis patients were collected. Every session consisted of two consecutive intra-dialysis measurements by the oscillometric monitors, each one performed simultaneously to an auscultatory measurement. A comparison with the intra-arterial method was performed as well. RESULTS: When compared with an in vivo data set previously collected, the HD-BPM accuracy complied with required limits. Second, the internal repeatability with respect to the simulator was satisfactory (SD of the differences between device and simulator readings: HD-BPM: systolic = 5.7, diastolic = 4.2; BX-100: systolic = 4.2, diastolic = 5.5 mmHg). Moreover, the comparison between oscillometric and auscultatory methods during in vivo trial gave similar results for the two monitors, even if systolic pressure SD exceeds the limit recommended by ANSI/AAMI SP-10 (mean value of the differences +/- SD: HD-BPM: systolic = 0.5 +/- 9.0, diastolic = 1.5 +/- 6.9; BX-100: systolic = 3.1 +/- 8.2, diastolic = -2.0 +/- 7.6 mmHg). CONCLUSIONS: These data underline the importance of performing accuracy evaluations for BP monitors in the conditions where they normally work, by using well-accepted protocols.

Effects of acoustic stimulation on cardiovascular regulation during sleep.

The interaction of wake-sleep states and acoustic stimulation on cardiovascular regulation was studied on rats implanted with electroencephalogram and electromyogram electrodes and an arterial catheter. Mild acoustic stimuli (1000 Hz, 90 dB, 50-ms beeps) were administered during Wakefulness (W), non-rapid eye movement (NREM) sleep and REM sleep and the changes induced in heart period (HP, ms) and mean arterial pressure (MAP, mmHg) were analyzed. Two 30-s sequences of beat-to-beat HP and MAP values were considered before (I) and after (II) acoustic stimulation, respectively. By the effect of stimulation, state-dependent stimulus-locked HP and MAP oscillations were observed, HP oscillations being grossly parallel to the MAP ones but delayed with respect to MAP in the ascending part only; HP and MAP spontaneous fluctuations (HP and MAP variability) increased in NREM and REM sleep (but not in W); HP vs MAP correlation coefficient increased in an algebraic sense. These results show that 1) acoustic stimulation primarily affects the peripheral resistance, and secondarily, through the baroreceptor reflex, HP, thereby increasing the impact of peripheral versus centrally driven autonomic influences on the heart; 2) in NREM sleep, heart excitability is higher than requested by the baroreflex function; 3) cardiac variability is increased by acoustic stimulation during sleep (but not in W); this, in addition to the effects of point 2, may favor cardiac arrhythmias in NREM sleep. Thus, mild acoustic stimuli not perturbing cardiovascular regulation during W may create a specific risk factor during sleep in pathophysiologic conditions.