Patient blood management in the cardiac surgical setting: An updated overview.

In cardiac surgical patients it is a complex challenge to find the ideal balance between anticoagulation and hemostasis. Preoperative anemia and perioperative higher transfusion rates are related to increased morbidity and mortality. Patient blood management (PBM) is an evidence based patient specific individualized protocol used in the perioperative setting in order to reduce perioperative bleeding and transfusion rates and to improve patient outcomes. The three pillars of PBM in cardiac surgery consist of optimization of preoperative erythropoiesis and hemostasis, minimizing blood loss, and improving patient specific physiological reserves. This narrative review focuses on the challenges with special emphasis on PBM in the preoperative phase and intraoperative transfusion management and hemostasis in cardiac surgery patients. It is a "must" that PBM is a collaborative effort between anesthesiologists, surgeons, perfusionists, intensivists and transfusion laboratory teams. This review represents an up to date overview over "PBM in cardiac surgery patients".

Is "really conscious" sedation with solely an opioid an alternative to every day used sedation regimes for colonoscopies in a teaching hospital? Midazolam/fentanyl, propofol/alfentanil, or alfentanil only for colonoscopy: a randomized trial.

BACKGROUND: We investigated the satisfaction of patients and endoscopists and concurrently safety aspects of an "alfentanil only" and two clinically routinely used sedation regimes in patients undergoing colonoscopy in a teaching hospital. METHODS: One hundred and eighty patients were prospectively randomized in three groups: M (midazolam/fentanyl), A (alfentanil), and P (propofol/alfentanil); M and A were administered by an endoscopy nurse, P by an anesthesia nurse. Interventions, heart rate, saturation, electrocardiogram, noninvasive blood pressure, and expiratory CO2 were monitored using video assistance. After endoscopy, patients and gastroenterologists completed questionnaires about satisfaction. RESULTS: A high level of satisfaction was found in all groups, with patients in group P being more satisfied with their sedation experience (median 1.75, p < 0.001). Gastroenterologist satisfaction varied not significantly between the three alternatives. Patients in group A felt less drowsy, could communicate more rapidly than patients in both other groups, and met discharge criteria immediately after the end of the procedure. Respiratory events associated with sedation were observed in 43% patients in group M, 47% in group P, but only 13% in group A (p < 0.001). CONCLUSIONS: These results suggest that alfentanil could be an alternative for sedation in colonoscopy even in the setting of a teaching hospital. It results in satisfied patients easily taking up information, and recovering rapidly. Although one might expect to observe more respiratory depression with an "opioid only" sedation technique without involvement of anesthesia partners, respiratory events were less frequent than when other methods were used.

Analgesia without sedatives during colonoscopies: worth considering?

Colonoscopy is a proven method for bowel cancer screening and is often experienced as a painful procedure. Today, there are two main strategies to facilitate colonoscopy. First, deep sedation results in satisfied patients but increases sedation-associated risks and raises costs for healthcare providers. Second, there is the advocacy for colonoscopies without any form of sedation. This might be an option for a special group of patients, but does not hold true for everybody. Following Moerman's hypothesis: "If pain is the crucial point, why do we need sedation?" this review shows the analgesic options for a painless procedure, increasing success rates without increasing risk of sedation. There are two agents, with the potential to be a nearly ideal analgesic agent for colonoscopy: alfentanil and nitrous oxide (N(2)O). Administration of either substance causes the patient to be comfortable yet alert and facilitates a short turnover. Advantages of these drugs include rapid onset and offset of action, analgesic and anxiolytic effects, ease of titration to desired level, rapid recovery, and an excellent safety profile.

Effect of increasing doses of mannitol on mucus clearance in patients with bronchiectasis.

Bronchiectasis is characterised by hypersecretion and impaired clearance of mucus. A 400-mg dose of inhaled mannitol improves mucus clearance however, the effect of other doses is unknown. A total of 14 patients, aged 63.3+/-5.7 yrs, were studied on five visits. Mucus clearance at baseline and with mannitol (160, 320 and 480 mg) was measured using technetium-99m-sulphur colloid and imaging with a gamma camera over 45 min, followed by a further 30 min involving 100 voluntary coughs. A control study assessed the effect of cough provoked by mannitol during the intervention. Whole right lung clearance over 45 min was 4.7+/-1.2 and 10.6+/-2.6% on baseline and control days, respectively, and increased to 16.7+/-4.2, 22.8+/-4.2 and 31+/-4.7% with 160, 320 and 480 mg mannitol, respectively. Clearance over 45 min with 480 mg mannitol was greater than clearance with 320 and 160 mg. Total clearance over 75 min, after mannitol administration and voluntary coughs, was 36.1+/-5.5, 40.9+/-5.6 and 46.0+/-5.2% with 160, 320 and 480 mg mannitol, respectively, all significantly different from baseline (24.1+/-6.0%) and control (13.1+/-3.0%). Total clearance over 75 min with 480 mg mannitol was greater compared with 160 mg. In conclusion, mucus clearance increases with increasing doses of mannitol and can be further increased by cough in patients with bronchiectasis.

In vivo imaging of nicotinic receptor upregulation following chronic (-)-nicotine treatment in baboon using SPECT.

To quantify changes in neuronal nAChR binding in vivo, quantitative dynamic SPECT studies were performed with 5-[(123)I]-iodo-A-85380 in baboons pre and post chronic treatment with (-)-nicotine or saline control. Infusion of (-)-nicotine at a dose of 2.0 mg/kg/24h for 14 days resulted in plasma (-)-nicotine levels of 27.3 ng/mL. This is equivalent to that found in an average human smoker (20 cigarettes a day). In the baboon brain the regional distribution of 5-[(123)I]-iodo-A-85380 was consistent with the known densities of nAChRs (thalamus > frontal cortex > cerebellum). Changes in nAChR binding were estimated from the volume of distribution (V(d) ) and binding potential (BP) derived from 3-compartment model fits. In the (-)-nicotine treated animal V(d) was significantly increased in the thalamus (52%) and cerebellum (50%) seven days post cessation of (-)-nicotine treatment, suggesting upregulation of nAChRs. The observed 33% increase in the frontal cortex failed to reach significance. A significant increase in BP was seen in the thalamus. In the saline control animal no changes were observed in V(d) or BP under any experimental conditions. In this preliminary study, we have demonstrated for the first time in vivo upregulation of neuronal nAChR binding following chronic (-)-nicotine treatment.

The 24-h effect of mannitol on the clearance of mucus in patients with bronchiectasis.

STUDY OBJECTIVE: To investigate the acute effect of mannitol on the clearance of mucus, and (1) the 24-h mucus retention, and (2) the mucus clearance rate and lung function 24 h after inhalation of a single dose of mannitol. DESIGN: Clearance of mucus was measured on 3 consecutive days using (99m)Tc-sulfur colloid radioaerosol and a gamma camera. INTERVENTIONS: Mannitol, 330 +/- 68 mg (mean+/- SD), was inhaled using a dry powder inhaler only on day 2. PATIENTS: Eight patients with bronchiectasis (age range, 29 to 70 years). MEASUREMENTS AND RESULTS: On each day, lung images were collected over 2 h and at 24 h. Key findings of the study are as follows: (1) the 24-h retention of mucus was reduced the day after mannitol had been inhaled, compared to the day without mannitol (day 1) in the whole right lung (57.6 +/- 6.2% vs 68.1 +/- 5.9%), central (47.5 +/- 6.7% vs 56.9 +/- 6.5%), intermediate (61.7 +/- 5.6% vs 73.8 +/- 5.5%), and peripheral regions (70.9 +/- 4.3% vs 86.6 +/- 4.6%)(p < 0.02); and (2) mannitol helped patients clear mucus within 2 h that might otherwise take up to 24 h, from the whole right lung and defined regions. However, clearance over 60 min measured 24 h after mannitol inhalation was not significantly different to baseline clearance without mannitol (8.7 +/- 1.9% on day 1 vs 9.7 +/- 3.7% 24 h after mannitol; p > 0.8). The patients maintained the same lung function the day before and after mannitol had been inhaled: FEV(1) (percent predicted), 79 +/- 5 on day 1 vs 80 +/- 5 on day 3; and forced expiratory flow, midexpiratory phase (percent predicted), 50 +/- 6 on day 1 vs 51 +/- 6 on day 3; p > 0.6). CONCLUSIONS: Mannitol inhalation acutely increases clearance of mucus, and this effect extends beyond the acute study period, resulting in decreased mucus retention at 24 h.

Regional mucociliary clearance in patients with cystic fibrosis.

This paper reports on a large retrospective analysis of mucociliary clearance (MCC) studies in a group of 59 patients with cystic fibrosis (CF) and 17 age-matched healthy subjects. As many of the CF patients were studied on multiple occasions, a total of 184 patient studies are presented. MCC was measured using a radioaerosol and gamma camera technique. In addition to whole lung clearance, MCC was measured from the central, intermediate, peripheral, basal, mid and apical regions of the lung. MCC was markedly decreased in the CF patient group. Not only was whole lung clearance (14.2 +/- 1.4% vs. 28.0 +/- 3.7%) impaired, but also clearance from the central (19.1 +/- 1.9% vs. 35.6 +/- 4.3%), intermediate (10.7 +/- 1.6% vs. 25.5 +/- 3.7%), apical (12.4 +/- 2.6% vs. 31.6 +/- 4.6%) and mid (14.0 +/- 1.9% vs. 30.4 +/- 4.0%) regions. Attempts were made to identify factors that may have influenced MCC in both the normal subjects and CF patients. Age, gender, body mass index, patient genotype, penetration index, spontaneous cough, and various lung function parameters were entered into a stepwise multiple regression model, but none of the factors proved to be statistically important in determining MCC. Both intrasubject repeatability and intersubject variability estimates are presented for the patients and normal subjects that had multiple studies. The values were found to be remarkably similar for both CF patients and normal subjects and for both intra- and intersubject repeatability. With marked deviation from normal ranges and good repeatability, the measurement of MCC in CF patients would seem to be a valuable outcome measure for clinical trials involving new pharmaceuticals and physical therapy designed to improve removal of secretions from the airways.

Effect of a short course of rhDNase on cough and mucociliary clearance in patients with cystic fibrosis.

The aim of the study was to measure the effect of a short course of recombinant human deoxyribonuclease I (rhDNase) on ciliary and cough clearance in a group of cystic fibrosis patients, using a radioaerosol and gamma camera technique. Patients were initially randomized to receive either rhDNase (2.5 mg qd) or placebo. Following the measurement of baseline clearance, patients were given a 7-day course of either rhDNase or placebo. The patient then returned on the seventh day for follow-up clearance measurements. This was followed by a 2-week washout period before the whole process was repeated with the alternative inhalation solution. On each of the study days, mucociliary clearance was initially measured for a period of 60 min (IC). This was followed by cough clearance (CC) measurements for 30 min, during which patients were requested to cough a total of 120 times. Post-cough clearance (PCC) was then measured for a further 60 min. Thirteen patients completed the study. Patients' age ranged between 18-38 years, and they had baseline values of FEV(1) of 27-103% of predicted values. Following completion of the course of rhDNase, there was a mean percent increase from baseline of 7.5% for FEV(1) and 5.4% for FVC% (P = 0. 03). There was a small, nonsignificant increase in IC (6.2 +/- 3.6%) on the rhDNase arm compared with the placebo arm (-2.3 +/- 2.9%), P = 0.1. No changes were seen in either CC (1.0 +/- 3.2% [rhDNase] vs. 1.9 +/- 2.4% [placebo], P = 0.9) or PCC (-0.7 +/- 1.5% [rhDNase] vs. 0.9 +/- 1.7% [placebo], P = 0.3). Patients who achieved a 10% or greater improvement in FEV(1) (n = 5) in response to rhDNase did not show any greater change in clearance than nonresponders. In conclusion, we were unable to demonstrate any improvements in either ciliary or cough clearance in response to a short course of rhDNase. The mechanism of action of this drug in vivo remains uncertain.

The effect of inhaled mannitol on bronchial mucus clearance in cystic fibrosis patients: a pilot study.

It has been postulated that hypertonic saline (HS) might impair the antimicrobial effects of defensins within the airways. Alternative non-ionic osmotic agents such as mannitol may thus be preferable to HS in promoting bronchial mucus clearance (BMC) in patients with cystic fibrosis (CF). This study reports the effect of inhalation of another osmotic agent, dry powder Mannitol (300 mg), compared with its control (empty capsules plus matched voluntary cough) and a 6% solution of HS on BMC in 12 patients with cystic fibrosis (CF). Mucus clearance was measured using a radioaerosol/gamma camera technique. Post-intervention clearance was measured for 60 min, followed by cough clearance for 30 min. Neither mannitol nor HS improved BMC during the actual intervention period compared with their respective controls. However during the post-intervention measurement there was a significant improvement in BMC for both the mannitol (8.7+/-3.3% versus 2.8+/-0.7%) and HS (10.0+/-2.3% versus 3.5+/-0.8%). There was also a significant improvement in cough clearance with the Mannitol (9.7+/-2.4%) compared with its control (2.5+/-0.8%). Despite premedication with a bronchodilator, a small fall in forced expiratory volume in one second (FEV1) was seen immediately after administration of both the mannitol (7.3+/-2.5%) and HS (5.8+/-1.2%). Values of FEV1 returned to baseline by the end of the study. Inhaled mannitol is a potential mucoactive agent in cystic fibrosis patients. Further studies are required to establish the optimal dose and the long-term effectiveness of mannitol.

Inhalation of dry powder mannitol improves clearance of mucus in patients with bronchiectasis.

Bronchiectasis is a disease characterized by hypersecretion and retention of mucus requiring physical and pharmacologic treatment. Recently we reported that inhalation of dry powder mannitol markedly increases mucociliary clearance (MCC) in asthmatic and in healthy subjects (Daviskas, E., S. D. Anderson, J. D. Brannan, H. K. Chan, S. Eberl, and G. Bautovich. 1997. Inhalation of dry-powder mannitol increases mucociliary clearance. Eur. Respir. J. 10:2449-2454). In this study we investigated the effect of mannitol on MCC in patients with bronchiectasis. Eleven patients 40 to 62 yr of age inhaled mannitol (approximately 300 mg) from a Dinkihaler. MCC was measured over 90 min, in the supine position, on three occasions involving: mannitol or control or baseline, using a radioaerosol technique. On the control day patients reproduced the breathing maneuvers and the number of coughs induced by the mannitol. Mannitol significantly increased MCC over the 75 min from the start of the intervention compared with control and baseline in the whole right lung, central, and intermediate region. Mean (+/- SEM) clearance with mannitol was 34.0 +/- 5.0% versus 17.4 +/- 3.8% with control and 11.7 +/- 4.4% with baseline in the whole right lung (p < 0.0001). The mean number of coughs induced by mannitol was 49 +/- 11. In conclusion, inhalation of dry powder mannitol increased clearance of mucus and thus has the potential to benefit patients with bronchiectasis.

Simultaneous emission and transmission measurements for attenuation correction in whole-body PET.

UNLABELLED: We describe a methodology for measuring and correcting for attenuation in whole-body PET using simultaneous emission and transmission (SET) measurements. METHODS: The main components of the methodology are: (a) sinogram windowing of low activity (< or = 50 MBq) rotating 68Ge/Ga rod sources, (b) segmented attenuation correction (SAC) and (c) maximum likelihood reconstruction using the ordered subsets EM (OS-EM) algorithm. The methods were implemented on a whole-body positron emission tomograph. Quantitative accuracy and the signal-to-noise ratio (SNR) were measured for a thorax-tumor phantom as functions of acquisition time (range: 2-20 min per position). RESULTS: When a typical rod source activity (200 MBq 68Ge/Ga) was used, emission SNR was 60% lower in simultaneous than in separate measurements. The difference was only 14% when the rods contained 45 MBq 68Ge/Ga. The SNR was further improved by SAC in conjunction with OS-EM reconstruction and the relative gain increased with increasing acquisition time. Quantitative estimates of tumor, liver and lung radioactivity agreed with values obtained from a separate high count measurement to within 8%, independent of acquisition time. CONCLUSION: Attenuation correction of whole-body PET images is feasible using SET measurements. There is good quantitative agreement with conventional methods and increased noise is offset by the use of SAC and OS-EM reconstruction.

Use of technetium-HMPAO to demonstrate changes in cerebral blood flow reserve following carotid endarterectomy.

Cerebral perfusion through stenosed internal carotid arteries is usually maintained by autoregulation. However, flow reserve may be reduced, suggesting hemodynamically significant stenosis, and such reduction should be improved by carotid endarterectomy. This concept was studied in 20 subjects with unilateral internal carotid artery stenosis (major stenosis greater than or equal to 70%, minor stenosis less than or equal to 50%). Thirteen had experienced recent transient ischemic attacks and seven had no definite focal symptoms. Subjects underwent Tc-HMPAO cerebral SPECT during acetazolamide dysautoregulation before and after internal carotid endarterectomy. Nine (45%) had perfusion defects that improved after surgery, suggesting surgery had improved cerebral flow reserve. Seven had defects that did not improve after surgery. Four had worsened or new defects after surgery, suggesting perioperative infarcts. The relatively large proportion of patients with improved cerebral blood flow reserve after surgery suggests that this technique may have a significant role to play in assessing which patients might benefit from carotid endarterectomy.

Cerebral perfusion defects, dysautoregulation and carotid stenosis.

Single Photon Emission Computed Tomography (SPECT), imaging of cerebral blood flow was carried out in ten patients with haemodynamically significant carotid stenosis. Before and after carotid endarterectomy each patient was investigated by 3--dimensional SPECT brain scanning using technetium--hexamethyl propyleneamine oxine (99 mTcHMPAO, ceretec). Brain blood flow was normal before and after operation in 3 patients whose autoregulation was kept intact. Seven patients received acetazolamide to limit cerebral vascular reactivity and in four of these, preoperative perfusion defects were visible. After carotid endarterectomy the ipsilateral perfusion defects were abolished and it is concluded that carotid stenosis can reduce perfusion in the dysautoregulation brain and that carotid reconstruction can restore normal flow.