Comparison of forces acting on maxillary incisors during tracheal intubation with different laryngoscopy techniques: a blinded manikin study.

Dental trauma is a common complication of tracheal intubation. As existing evidence is insufficient to validly assess the impact of different laryngoscopy techniques on the incidence of dental trauma, the force exerted onto dental structures during tracheal intubation was investigated. An intubation manikin was equipped with hidden force sensors in all maxillary incisors. Dental force was measured while 104 anaesthetists performed a series of tracheal intubations using direct laryngoscopy with a Macintosh blade, and videolaryngoscopy with a C-MAC® , or the hyperangulated GlideScope® or KingVision® laryngoscopes in both normal and difficult airway conditions. A total of 624 tracheal intubations were analysed. The median (IQR [range]) peak force of direct laryngoscopy in normal airways was 21.1 (14.0-32.8 [2.3-127.6]) N and 29.3 (17.7-44.8 [3.3-97.2]) N in difficult airways. In normal airways, these were lower with the GlideScope and KingVision hyperangulated laryngoscopes, with a reduction of 4.6 N (p = 0.006) and 10.9 N (p < 0.001) compared with direct laryngoscopy, respectively. In difficult airways, these were lower with the GlideScope and KingVision hyperangulated laryngoscopes, with a reduction of 9.8 N (p < 0.001) and 17.6 N (p < 0.001) compared with direct laryngoscopy, respectively. The use of the C-MAC did not have an impact on the median peak force. Although sex of anaesthetists did not affect peak force, more experienced anaesthetists generated a higher peak force than less experienced providers. We conclude that hyperangulated videolaryngoscopy was associated with a significantly decreased force exerted on maxillary incisors and might reduce the risk for dental injury in clinical settings.

Correction to: Protective ventilation with high versus low positive end-expiratory pressure during one-lung ventilation for thoracic surgery (PROTHOR): study protocol for a randomized controlled trial.

After publication of the original article [1], the authors have notified us that two of the collaborator first and last names have been inverted in the "PROTHOR Investigators" table.

Protective ventilation with high versus low positive end-expiratory pressure during one-lung ventilation for thoracic surgery (PROTHOR): study protocol for a randomized controlled trial.

BACKGROUND: Postoperative pulmonary complications (PPC) may result in longer duration of in-hospital stay and even mortality. Both thoracic surgery and intraoperative mechanical ventilation settings add considerably to the risk of PPC. It is unclear if one-lung ventilation (OLV) for thoracic surgery with a strategy of intraoperative high positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM) reduces PPC, compared to low PEEP without RM. METHODS: PROTHOR is an international, multicenter, randomized, controlled, assessor-blinded, two-arm trial initiated by investigators of the PROtective VEntilation NETwork. In total, 2378 patients will be randomly assigned to one of two different intraoperative mechanical ventilation strategies. Investigators screen patients aged 18 years or older, scheduled for open thoracic or video-assisted thoracoscopic surgery under general anesthesia requiring OLV, with a maximal body mass index of 35 kg/m2, and a planned duration of surgery of more than 60 min. Further, the expected duration of OLV shall be longer than two-lung ventilation, and lung separation is planned with a double lumen tube. Patients will be randomly assigned to PEEP of 10 cmH2O with lung RM, or PEEP of 5 cmH2O without RM. During two-lung ventilation tidal volume is set at 7 mL/kg predicted body weight and, during OLV, it will be decreased to 5 mL/kg. The occurrence of PPC will be recorded as a collapsed composite of single adverse pulmonary events and represents the primary endpoint. DISCUSSION: PROTHOR is the first randomized controlled trial in patients undergoing thoracic surgery with OLV that is adequately powered to compare the effects of intraoperative high PEEP with RM versus low PEEP without RM on PPC. The results of the PROTHOR trial will support anesthesiologists in their decision to set intraoperative PEEP during protective ventilation for OLV in thoracic surgery. TRIAL REGISTRATION: The trial was registered in clinicaltrials.gov ( NCT02963025 ) on 15 November 2016.

Oesophageal Doppler guided goal-directed haemodynamic therapy in thoracic surgery - a single centre randomized parallel-arm trial.

BACKGROUND: Postoperative pulmonary and renal complications are frequent in patients undergoing lung surgery. Hyper- and hypovolaemia may contribute to these complications. We hypothesized that goal-directed haemodynamic management based on oesophageal Doppler monitoring would reduce postoperative pulmonary complications in a randomized clinical parallel-arm trial. METHODS: One hundred patients scheduled for thoracic surgery were randomly assigned to either standard haemodynamic management (control group) or goal-directed therapy (GDT group) guided by an oesophageal Doppler monitoring-based algorithm. The primary endpoint was postoperative pulmonary complications, including spirometry. Secondary endpoints included haemodynamic variables, renal, cardiac, and neurological complications, and length of hospital stay. The investigator assessing outcomes was blinded to group assignment. RESULTS: Forty-eight subjects of each group were analysed. Compared to the control group, fewer subjects in the GDT group developed postoperative pulmonary complications (6 vs. 15 patients; P = 0.047), while spirometry did not differ between groups. Compared to the control group, patients of the GDT group showed higher cardiac index (2.9 vs. 2.1 [l min - 1 m - 2 ]; P < 0.001) and stroke volume index (43 vs. 34 [ml m 2 ]; P < 0.001) during surgery. Renal, cardiac and neurological complications did not differ between groups. Length of hospital stay was shorter in the GDT compared to the control group (9 vs. 11 days; P = 0.005). CONCLUSIONS: Compared to standard haemodynamic management, oesophageal Doppler monitor-guided GDT was associated with fewer postoperative pulmonary complications and a shorter hospital stay. CLINICAL TRIAL REGISTRATION.: The study was registered in the German Clinical Trials Register (DRKS 00006961). https://drks-neu.uniklinik-freiburg.de/drks_web/.

[A Germany-wide survey on anaesthesia in thoracic surgery]. / Deutschlandweite Umfrage zur Thoraxanästhesie.

BACKGROUND/OBJECTIVE: This study's objective was to evaluate current thoracic anaesthesia practice in Germany and to quantify potential differences depending on the hospital's level of care. MATERIALS AND METHODS: A four-part online survey containing 28 questions was mailed to all anaesthesiology department chairs (n = 777) registered with the German Society of Anaesthesiology and Intensive Care Medicine. RESULTS: The general response rate was 31.5 % (n = 245). High monthly volumes (>50 operations/month) of intrathoracic procedures, performed by specialized thoracic surgeons are mostly limited to hospitals of maximum care, university hospitals, and specialized thoracic clinics. In hospitals with a lower level of care, intrathoracic operations occur less frequently (1-5/month) and are commonly performed by general (69.3 %) rather than thoracic surgeons (15.4 %). Video-assisted thoracic surgeries are the most invasive intrathoracic procedures for most hospitals with a low level of care (61.5 %). Extended resections and pneumonectomies occur mainly in hospitals of maximum care and university hospitals. Thoracic anaesthesia is primarily performed by consultants or senior physicians (59.9 %). The double lumen tube (91.4 %) is the preferred method to enable one-lung ventilation (bronchial blockers: 2.7 %; missing answer: 5.9 %). A bronchoscopic confirmation of the correct placement of a double lumen tube is considered mandatory by 87.7 % of the respondents. Bronchial blockers are available in 64.7 % of all thoracic anaesthesia departments. While CPAP-valves for the deflated lung are commonly used (74.9 %), jet-ventilators are rarely accessible, especially in hospitals with a lower level of care (15.4 %). Although general algorithms for a difficult airway are widely available (87.7 %), specific recommendations for a difficult airway in thoracic anaesthesia are uncommon (4.8 %). Laryngeal mask airways (90.9 %) and videolaryngoscopy (88.8 %) are the primary adjuncts in store for a difficult airway. While hospitals with a lower level of care admitted patients routinely (92.3 %) to an intensive care unit after thoracic surgery, larger clinics used the postanaesthesia recovery room (12.5 %) and intermediate care units (14.6 %) more frequently for further surveillance. Thoracic epidural catheters (85.6 %) are predominantly chosen for peri- and postoperative analgesia, in contrast to paravertebral blockade (single shot: 8.6 %; catheter: 8.0 %) (multiple answers possible). Ultrasound is generally accessible (84.5 %) and mostly employed for the placement of central venous (81.3 %) and arterial (43.9 %) lines as well as a diagnostic tool for pulmonary pathology (62.0 %). CONCLUSION: The study reveals considerable differences in the anaesthetic practice in thoracic surgery. These focus mostly on the postoperative surveillance, the availability of bronchial blockers, and the use of regional anaesthetic techniques. Furthermore, it is evident that specific algorithms are needed for the difficult airway in thoracic anaesthesia. A recommendation for the high-tech work environment of thoracic anaesthesia could enhance the structural quality and optimize patient outcomes. Independent of a hospital's level of care, uniform requirements could help establish national quality standards in thoracic anaesthesia.

Double-lumen tubes and auto-PEEP during one-lung ventilation.

BACKGROUND: Double-lumen tubes (DLT) are routinely used to enable one-lung-ventilation (OLV) during thoracic anaesthesia. The flow-dependent resistance of the DLT's bronchial limb may be high as a result of its narrow inner diameter and length, and thus potentially contribute to an unintended increase in positive end-expiratory pressure (auto-PEEP). We therefore studied the impact of adult sized DLTs on the dynamic auto-PEEP during OLV. METHODS: In this prospective clinical study, dynamic auto-PEEP was determined in 72 patients undergoing thoracic surgery, with right- and left-sided DLTs of various sizes. During OLV, air trapping was provoked by increasing inspiration to expiration ratio from 1:2 to 2:1 (five steps). Based on measured flow rate, airway pressure (Paw) and bronchial pressure (Pbronch), the pressure gradient across the DLT (ΔPDLT) and the total auto-PEEP in the respiratory system (i.e. the lungs, the DLT and the ventilator circuit) were determined. Subsequently the DLT's share in total auto-PEEP was calculated. RESULTS: ΔPDLT was 2.3 (0.7) cm H2O over the entire breathing cycle. At the shortest expiratory time the mean total auto-PEEP was 2.9 (1.5) cm H2O (range 0-5.9 cm H2O). The DLT caused 27 to 31% of the total auto-PEEP. Size and side of the DLT's bronchial limb did not impact auto-PEEP significantly. CONCLUSIONS: Although the DLT contributes to the overall auto-PEEP, its contribution is small and independent of size and side of the DLT's bronchial limb. The choice of DLT does not influence the risk of auto-PEEP during OLV to a clinically relevant extent. CLINICAL TRIAL REGISTRATION: DRKS00005648.

[Thoracic epidural catheter: reasonable or over-instrumentation?]. / Thorakaler Periduralkatheter: Sinnvoll oder Überinstrumentierung?

The efficient and persisting treatment of the pain accompanying thoracic surgery is fundamental and beneficial for patients, since severe postoperative pulmonary complications and the incidence of chronic pain will be reduced. In this review the role of thoracic epidural analgesia in preventing and treating pain after thoracic surgery will be discussed critically and alternative strategies presented.

Protective effects of inhaled carbon monoxide in pig lungs during cardiopulmonary bypass are mediated via an induction of the heat shock response.

BACKGROUND: Cardiopulmonary bypass (CPB) may cause acute lung injury leading to increased morbidity and mortality after cardiac surgery. Preconditioning by inhaled carbon monoxide reduces pulmonary inflammation during CPB. We hypothesized that inhaled carbon monoxide mediates its anti-inflammatory and cytoprotective effects during CPB via induction of pulmonary heat shock proteins (Hsps). METHODS: Pigs were randomized either to a control group, to standard CPB, to carbon monoxide+CPB, or to quercetin (a flavonoid and unspecific inhibitor of the heat shock response)+control, to quercetin+CPB, and to quercetin+carbon monoxide+CPB. In the carbon monoxide groups, lungs were ventilated with 250 ppm carbon monoxide in addition to standard ventilation before CPB. At various time points, lung biopsies were obtained and pulmonary Hsp and cytokine concentrations determined. RESULTS: Haemodynamic parameters were largely unaffected by CPB, carbon monoxide inhalation, or administration of quercetin. Compared with standard CPB, carbon monoxide inhalation significantly increased the pulmonary expression of the Hsps 70 [27 (SD 3) vs 69 (10) ng ml(-1) at 120 min post-CPB, P<0.05] and 90 [0.3 (0.03) vs 0.52 (0.05) after 120 min CPB, P<0.05], induced the DNA binding of heat shock factor-1, reduced interleukin-6 protein expression [936 (75) vs 320 (138) at 120 min post-CPB, P<0.001], and decreased CPB-associated lung injury (assessed by lung biopsy). These carbon monoxide-mediated effects were inhibited by quercetin. CONCLUSIONS: As quercetin, a Hsp inhibitor, reversed carbon monoxide-mediated pulmonary effects, we conclude that the anti-inflammatory and protective effects of preconditioning by inhaled carbon monoxide during CPB in pigs are mediated by an activation of the heat shock response.

[Epidural analgesia in thoracic surgery--optimising postoperative rehabilitation]. / Einsatz der epiduralen Analgesie in der konventionellen Thoraxchirurgie--Optimierung der postoperativen Rehabilitation.

INTRODUCTION: A multimodal perioperative therapy strategy (fast-track) decreases the morbidity of general thoracic interventions and increases postoperative reconvalescence after lung resections. Thoracic surgery is associated with relevant pain and sufficient pain relief is essential for postoperative recovery. Epidural analgesia leads to adequate pain control with only minor side effects and complications and can therefore be a reasonable supplementation in a modern fast-track setting. The purpose of this study was to evaluate the benefits and risks of an epidural catheter placed prior to surgery and to analyse the postoperative recovery of patients undergoing thoracic surgery. METHODS: 277 patients undergoing pulmonary resection through an anterolateral thoracotomy were included in our study. Epidural analgesia was carried out through placement of an epidural catheter equipped with Naropine-Sufenta perfusor prior to surgery. Perioperative clinical parameters as well as postoperative management were evaluated. Pain intensity was documented using the visual analogue scale (VAS). Side effects and complications were summarised in five grades of severity (1-5). Insufficient pain relief was recognised when a VAS > 4 was registered. RESULTS: Median patient age was 59 years, the male / female relation was precisely 2 : 1, on average epidural analgesia was carried out for 4.9 days. Severe complications (grade 4 or 5) were not found. In 37 % of the cases, minor complications and side effects were found, in 1 % clinical relevant complications led to further diagnostic measures. For sufficient pain relief, 10 % of the studied population needed additional treatment with systemic opioids. CONCLUSION: We have shown that epidural analgesia in patients undergoing thoracotomy leads to sufficient pain control with only minor disadvantages and complications. These are easily mastered without expensive diagnostic or therapeutic interventions. Therefore, epidural analgesia is a safe and helpful tool for increased postoperative recovery within a modern fast-track setting.

Electrical impedance tomography to confirm correct placement of double-lumen tube: a feasibility study.

BACKGROUND: Double-lumen tubes (DLTs) are frequently used to establish one-lung ventilation (OLV). Their correct placement is crucial. We hypothesized that electrical impedance tomography (EIT) reliably displays distribution of ventilation between left and right lung and may thus be used to verify correct DLT placement online. METHODS: Regional ventilation was studied by EIT in 40 patients requiring insertion of left-sided DLTs for OLV during thoracic surgery. EIT was recorded during two-lung ventilation before induction of anaesthesia and after DLT placement, and during OLV in the supine and subsequently in the lateral position. EIT measurements were made before and after verification of correct DLT placement by fibreoptic bronchoscopy (FOB). RESULTS: EIT accurately displayed distribution of ventilation between left and right lung online. All cases (n=5) of initially misplaced DLTs in the contralateral right main bronchus were detected by EIT. However, EIT did not allow prediction of FOB-detected endobronchial cuff misplacement requiring DLT repositioning. Furthermore, after DLT repositioning, distribution of ventilation, as assessed by EIT, did not change significantly (all P>0.5). CONCLUSIONS: This study demonstrates that EIT enables accurate display of left and right lung ventilation and, thus, non-invasive online recognition of misplacement of left-sided DLTs in the contralateral main bronchus. However, as distribution of ventilation did not correlate with endobronchial cuff placement, EIT cannot replace FOB in the routine control of DLT position.

Comparison of cellular functionality of human mesenchymal stromal cells and PBMC.

BACKGROUND: Human mesenchymal stromal cells (MSC) and PBMC play significant roles in repair processes following inflammation. Mechanisms of recruitment are still under investigation. METHODS AND RESULTS: MIP-1alpha induced the chemotactic migration of MSC but not of PBMC. Correlating with this, 7.7% of MSC expressed the chemokine receptor CCR-1, as shown by FACS analysis. In contrast, PBMC did not express CCR-1 or CCR-2 but did express CXCR-4 (81.9%) and CCR-7 (42.2%). Setum induced the chemotaxis of both cell types, and zymosan activation increased the migration of PBMC but not of MSC. Corresponding with this, C5a induced the migration of PBMC but not of MSC. Dose-dependent and -specific adhesion to fibronectin, fibrinogen, collagen type I and collagen type II could be demonstrated for MSC; in contrast, PBMC did not adhere to any of the investigated proteins. Real-time PCR of receptor expression revealed a 12.2-fold higher expression of alphav in MSC compared with PBMC. Incubation of MSC with tumor necrosis factor-alpha (TNFalpha) induced NFkappaB activation and increased the chemotactic response to serum and adhesion to fibronedtin. DISCUSSION: Chemotaxis and adhesion are crucial and differing cell fundtons of MSC and PBMC.

Prospective, randomized cost analysis of anesthesia with remifentanil combined with propofol, desflurane or sevoflurane for otorhinolaryngeal surgery.

BACKGROUND: In the era of cost containment, cost analysis should demonstrate the cost-effectiveness of new anesthetic drugs. METHODS: This single-blind, prospective, randomized study compared the costs of three remifentanil (REM)-based anesthetic techniques with a conventional one in 120 patients undergoing otorhinolaryngeal surgery. The patients were randomized (n=30 each group) to either receive a combination of REM with propofol, desflurane or sevoflurane, or a conventional anesthetic with thiopentone, alfentanil, isoflurane and N2O. RESULTS: The costs for anesthetic and nonanesthetic drugs and for disposables were twice as high in the three REM-based groups as in the conventional group (REM/PRO 0.51 Euro;/min, REM/DES 0.42 Euro;/min, and REM/SEVO 0.41 Euro;/min vs. 0.18 Euro;/min in the ALF/ISO/N2O group; P<0.05). Wastage of intravenous drugs accounted for up to 40% of total costs. In all REM groups, early recovery was predictably faster and more complete (P<0.05). Patient satisfaction was equally high (90-97%) in all groups, with less nausea in the REM/PRO group. CONCLUSION: This study demonstrates that REM-based anesthetic techniques are more expensive than a conventional technique using alfentanil, isoflurane and N2O. This is the result of higher costs of anesthetic and nonanesthetic drugs and of disposables. The wastage of intravenous drugs contributes considerably to these costs.

Lipopeptide adjuvants: monitoring and comparison of P3CSK4- and LPS-induced gene transcription.

Bacteria-derived synthetic lipoproteins constitute potent macrophage activators in vivo and are effective stimuli, enhancing the immune response especially with respect to low or non-immunogenic compounds. N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2R,S)-propyl]-(R)-cysteinyl-seryl-(lysyl)3-lysine (P3CSK4), exhibiting one of the most effective lipopeptide derivatives, represents a highly efficient immunoadjuvant in parenteral, oral, nasal and genetic immunization either in combination with or after covalent linkage to antigen. In order to further elucidate its molecular mode of action with respect to the transcriptional level, we focused our investigations on the P3CSK4-induced modulation of gene transcription. We could show that P3CSK4 activates/represses an array of at least 140 genes partly involved in signal transduction and regulation of the immune response. P3CSK4 activates the expression of tumor suppressor protein p53 (p53), c-rel, inhibitor of nuclear factor kappa B (NFkappaB) alpha (IkappaB alpha), type 2 (inducible) nitric oxide (NO) synthase (iNOS), CD40-LR, intercellular adhesion molecule-1 (ICAM-1) and interleukin 1/6/15 (IL-1/6/15). We detected no activation of heat shock protein (HSP) 27, 60, 84 and 86, osmotic stress protein 94 (Osp 94), IL-12, extracellular signal-regulated protein kinase 1 (ERK1), p38 mitogen activated protein (MAP)-kinase (p38), c-Jun NH2-terminal kinase (JNK), signal transducer and activator of transcription 1 (STAT1), CD14 and caspase genes. Furthermore, we monitored inhibition of STAT6, Janus kinase 3 (Jak3) and cyclin D1/D3 gene transcription after stimulating bone marrow-derived macrophages (BMDM) with lipopeptide. In addition, we monitored significant differences after lipopeptide and lipopolysaccharide (LPS) stimulation of bone marrow-derived murine macrophages. Our findings are of importance for further optimizing both conventional and genetic immunization, and for the development of novel synthetic vaccines.

Extracorporeal membrane oxygenation: a ten-year experience.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a supportive therapy used for severe acute respiratory distress syndrome (ARDS). We present outcome, clinical parameters, and complications in a cohort of 245 ARDS patients of whom 62 were treated with ECMO. METHODS: Data of all ARDS patients were prospectively collected between 1991 and 1999. Outcome and clinical parameters of patients treated with and without ECMO were evaluated. RESULTS: One hundred thirty-eight patients were referred from other hospitals, 107 were primarily located in our hospital. About one fourth of these patients were treated with ECMO. The survival rate was 55% in ECMO patients and 61% in non-ECMO patients. CONCLUSIONS: ECMO is a therapeutic option for patients with severe ARDS, likely to increase survival. However, a randomized controlled study proving its benefit is still awaited. Until the development of a causal or otherwise superior therapy ECMO should be used in selected patients.

Recovery after anesthesia with remifentanil combined with propofol, desflurane, or sevoflurane for otorhinolaryngeal surgery.

UNLABELLED: Because no previous investigation has directly compared the combination of remifentanil (REM) and a hypnotic with that of REM and the newer volatile anesthetics, we studied recovery characteristics and patient satisfaction after the combination of REM with propofol (PRO), desflurane (DES), or sevoflurane (SEVO). One hundred twenty patients were randomly assigned to receive anesthesia with either REM/PRO, REM/DES, REM/SEVO, or thiopental/alfentanil/isoflurane/N(2)O (control group) for ear, nose, and throat surgery (n = 30 each). In the REM groups, the dosage of PRO (75 microg. kg(-1). min(-1)), and of DES or SEVO (0.5 minimum alveolar anesthetic concentration) was kept unchanged, and REM was titrated to hemodynamic response. The control group was managed according to standard practice. Early recovery (times to eye opening, extubation, and statement of name and date of birth) was predictably faster and more complete in the REM groups compared with the control group. However, late recovery (times to discharge from postanesthesia care unit and hospital) and overall patient satisfaction were not different among groups. No clinically relevant differences existed among the three REM groups. In conclusion, the combination of REM infusion with small-dose DES, SEVO, or PRO is characterized by predictably rapid, early recovery. However, late recovery and patient satisfaction are comparable to a conventional anesthetic technique. IMPLICATIONS: Remifentanil anesthesia, combined with small-dose propofol, desflurane, or sevoflurane, enables predictably fast and smooth early recovery after ear, nose, and throat surgery. Despite such faster, early recovery and less need for postoperative analgesic and antiemetic medication, late recovery was comparable among the remifentanil combination groups and the control group.

Immunostimulation by bacterial components: I. Activation Of macrophages and enhancement of genetic immunization by the lipopeptide P3CSK4.

Synthetic lipopeptides derived from the N-terminus of bacterial lipoprotein constitute potent macrophage activators and polyclonal B-lymphocyte stimulators. They are also efficient immunoadjuvants in parenteral, oral and nasal immunization either in combination with or after covalent linkage to an antigen. Here we show how alterations in the molecular structure influence their biological properties indicating P3CSK4 as one of the most active members of a lipopentapeptide fatty acid library. This compound resulted in a most pronounced macrophage stimulation as indicated by NO release, activation of NFkappaB translocation, and enhancement of tyrosine protein phosphorylation. Furthermore, P3CSK4 activates/represses an array of at least 140 genes partly involved in signal transduction and regulation of the immune response. Finally we have evidence that P3CSK4 constitutes an effective adjuvant for DNA immunizations, especially increasing weak humoral immune responses. Our findings are of importance for further optimizing both conventional and genetic immunization, and for the development of novel synthetic vaccines.

[Arterial hypertension: its impact on perioperative morbidity and mortality]. / Die arterielle Hypertonie: Ihre Bedeutung für die perioperative Morbidität und Mortalität.

Chronic hypertension is associated with structural as well as functional changes of the vasculature, in particular of the coronary, cerebral and renal circulation. It is important to realise that [1] functional changes are often the result of structural changes, [2] the longer lasting the hypertension, the slower and less complete the regression of structural changes, and [3] acute "normalisation" of arterial pressure in long-standing hypertension may initially induce functionally subnormal smooth muscle and/or cardiac activity because the structure of the cardiovascular system is adapted to function at elevated pressures. Despite a multitude of studies, the impact of hypertension on peri-operative morbidity and mortality remains controversial. There are as many studies seeming to suggest that preoperative hypertension correlates with adverse outcome as there are studies that fail to establish such a relationship. When looking at the combined evidence, one is inclined to conclude that hypertension is a predictor of "soft" outcomes (e.g. peri-operative myocardial ischaemia and transient post-operative neurologic deficit) rather than an independent predictor of "hard" outcomes (e.g. unstable angina, myocardial infarction and cardiac death). In view of lack of convincing outcome data, it is impossible to recommend a generally acceptable management strategy for the hypertensive patient. Although, in general, a gradual reduction of blood pressure over a period of weeks to months is the optimal therapeutic approach, we will be hard-pressed delaying surgery for the sole purpose of "better blood pressure control". With full appreciation and detailed knowledge of the pathophysiology of hypertension, combined with sophisticated haemodynamic monitoring and interventions in the peri-operative period, acutely anaesthetising an inadequately treated hypertensive patient will probably not adversely affect his outcome. Delaying surgery for additional work-up may possibly improve outcome in patients with target organ disease, evidence of secondary hypertension, in the most severe forms of hypertension or sudden-onset hypertension.

Inhaled nitric oxide reduces pulmonary transvascular albumin flux in patients with acute lung injury.

BACKGROUND: In acute lung injury, when pulmonary microvascular permeability is enhanced, transvascular fluid filtration mainly depends on pulmonary capillary pressure. Inhaled nitric oxide has been shown to decrease pulmonary capillary pressure. Therefore, the effect of inhaled nitric oxide at a concentration of 40 ppm on pulmonary transvascular albumin flux was studied in nine patients with acute lung injury. METHODS: Transvascular albumin flux was measured by a double radioisotope method using 99mTc-labeled albumin and 51Cr-labeled autologous red blood cells. Radioactivity of both isotopes was externally measured over the right lung by a gamma scanner and simultaneously in arterial blood. The normalized ratio of 99mTc/51Cr lung to 99mTc/51Cr blood (normalized index) was calculated. The normalized slope index which is the slope of the regression line of the normalized index versus time represents the accumulation rate of albumin in the interstitial space of the lungs. Normalized slope index and pulmonary capillary pressure were determined before, during, and after inhalation of 40 ppm nitric oxide. Pulmonary capillary pressure was estimated using the visual analysis of the pressure decay curve after pulmonary artery occlusion. RESULTS: Normalized slope index decreased from 0.0077 +/- 0.0054 min-1 (SD) off nitric oxide to -0.0055 +/- 0.0049 min-1 (P < 0.01) during nitric oxide and increased to 0.0041 +/- 0.0135 min-1 after nitric oxide. Pulmonary capillary pressure declined from 24 +/- 4 mmHg off nitric oxide to 21 +/- 4 mmHg during nitric oxide (P < 0.01), whereas pulmonary artery wedge pressure and cardiac output did not change. CONCLUSIONS: It is concluded that 40 ppm inhaled nitric oxide decreases pulmonary transvascular albumin flux in patients with acute lung injury. This effect may be the result of the decrease in pulmonary capillary pressure.