Optimization of anastomotic technique and gastric conduit perfusion with hyperspectral imaging and machine learning in an experimental model for minimally invasive esophagectomy.

INTRODUCTION: Esophagectomy is the mainstay of esophageal cancer treatment, but anastomotic insufficiency related morbidity and mortality remain challenging for patient outcome. Therefore, the objective of this work was to optimize anastomotic technique and gastric conduit perfusion with hyperspectral imaging (HSI) for total minimally invasive esophagectomy (MIE) with linear stapled anastomosis. MATERIAL AND METHODS: A live porcine model (n = 58) for MIE was used with gastric conduit formation and simulation of linear stapled side-to-side esophagogastrostomy. Four main experimental groups differed in stapling length (3 vs. 6 cm) and simulation of anastomotic position on the conduit (cranial vs. caudal). Tissue oxygenation around the anastomotic simulation site was evaluated using HSI and was validated with histopathology. RESULTS: The tissue oxygenation (ΔStO2) after the anastomotic simulation remained constant only for the short stapler in caudal position (-0.4 ± 4.4%, n.s.) while it was impaired markedly in the other groups (short-cranial: -15.6 ± 11.5%, p = 0.0002; long-cranial: -20.4 ± 7.6%, p = 0.0126; long-caudal: -16.1 ± 9.4%, p < 0.0001). Tissue samples from avascular stomach as measured by HSI showed correspondent eosinophilic pre-necrotic changes in 35.7 ± 9.7% of the surface area. CONCLUSION: Tissue oxygenation at the site of anastomotic simulation of the gastric conduit during MIE is influenced by stapling technique. Optimal oxygenation was achieved with a short stapler (3 cm) and sufficient distance of the simulated anastomosis to the cranial end of the gastric conduit. HSI tissue deoxygenation corresponded to histopathologic necrotic tissue changes. The experimental model with HSI and ML allow for systematic optimization of gastric conduit perfusion and anastomotic technique while clinical translation will have to be proven.

Intranasal cooling with or without intravenous cold fluids during and after cardiac arrest in pigs.

BACKGROUND: Intranasal balloon catheters circulated with cold saline have previously been used for the induction and maintenance of selective brain cooling in pigs with normal circulation. In the present study, we investigated the feasibility of therapeutic hypothermia initiation, maintenance and rewarming using such intranasal balloon catheters with or without addition of intravenous ice-cold fluids during and after cardiac arrest treatment in pigs. MATERIAL AND METHODS: Cardiac arrest was induced in 20 anaesthetised pigs. Following 8 min of cardiac arrest and 1 min of cardiopulmonary resuscitation (CPR), cooling was initiated after randomisation with either intranasal cooling (N) or combined with intravenous ice-cold fluids (N+S). Hypothermia was maintained for 180 min, followed by 180 min of rewarming. Brain and oesophageal temperatures, haemodynamic variables and intracranial pressure (ICP) were recorded. RESULTS: Brain temperatures reductions after cooling did not differ (3.8 +/- 0.7 degrees C in the N group and 4.3 +/- 1.5 degrees C in the N+S group; P=0.47). The corresponding body temperature reductions were 3.6 +/- 1.2 degrees C and 4.6 +/- 1.5 degrees C (P=0.1). The resuscitation outcome was similar in both groups. Mixed venous oxygen saturation was lower in the N group after cooling and rewarming (P=0.024 and 0.002, respectively) as compared with the N+S group. ICP was higher after rewarming in the N group (25.2 +/- 2.9 mmHg; P=0.01) than in the N+S group (15.7 +/- 3.3 mmHg). CONCLUSIONS: Intranasal balloon catheters can be used for therapeutic hypothermia initiation, maintenance and rewarming during CPR and after successful resuscitation in pigs.

Intranasal selective brain cooling in pigs.

BACKGROUND: Special clinical situations where general hypothermia cannot be recommended but can be a useful treatment demand a new approach, selective brain cooling. The purpose of this study was to selectively cool the brain with cold saline circulating in balloon catheters introduced into the nasal cavity in pigs. MATERIAL AND METHODS: Twelve anaesthetised pigs were subjected to selective cerebral cooling for a period of 6 h. Cerebral temperature was lowered by means of bilaterally introduced nasal balloon catheters perfused with saline cooled by a heat exchanger to 8-10 degrees C. Brain temperature was measured in both cerebral hemispheres. Body temperature was measured in rectum, oesophagus and the right atrium. The pigs were normoventilated and haemodynamic variables were measured continuously. Acid-base and electrolyte status was measured hourly. RESULTS: Cerebral hypothermia was induced rapidly and within the first 20 min of cooling cerebral temperature was lowered from 38.1+/-0.6 degrees C by a mean of 2.8+/-0.6 to 35.3+/-0.6 degrees C. Cooling was maintained for 6 h and the final brain temperature was 34.7+/-0.9 degrees C. Concomitantly, the body temperature, as reflected by oesophageal temperature was decreased from 38.3+/-0.5 to 36.6+/-0.9 degrees C. No circulatory or metabolic disturbances were noted. CONCLUSIONS: Inducing selective brain hypothermia with cold saline via nasal balloon catheters can effectively be accomplished in pigs, with no major disturbances in systemic circulation or physiological variables. The temperature gradients between brain and body can be maintained for at least 6 h.

Measurement of exhaled volatile organic compounds from patients with chronic obstructive pulmonary disease (COPD) using closed gas loop GC-IMS and GC-APCI-MS.

Due to its high sensitivity, compact size and low cost ion mobility spectrometry (IMS) has the potential to become a point-of-care breath analyzer. Therefore, we developed a prototype of a compact, closed gas loop IMS with gas chromatographic (GC) pre-separation and high resolving power of R = 90. In this study, we evaluated the performance of this GC-IMS under clinical conditions in a COPD study to find correlations between VOCs (10 ppbv to 1 ppmv) and COPD. Furthermore, in order to investigate possible correlations between ultra-low concentrated breath VOCs (0.1 pptv to 1 ppbv) and COPD, a modified mass spectrometer (MS) with atmospheric pressure chemical ionization (APCI) and GC pre-separation (GC-APCI-MS) was used. The GC-IMS has been used in 58 subjects (21 smokers with moderate COPD, 12 ex-smokers with COPD, 16 healthy smokers and 9 non-smokers). GC-APCI-MS data were available for 94 subjects (21 smokers with moderate COPD, 25 ex-smokers with COPD, 25 healthy smokers and 23 non-smokers). For 44 subjects, a comparison between GC-IMS and GC-APCI-MS data could be performed. Due to service intervals, subject availability and corrupt data, patient numbers were different for GC-APCI-MS and GC-IMS measurements. Using GC-IMS, three VOCs have been found showing a significant difference between healthy controls and patients with COPD. In the GC-APCI-MS data, we only observed one distinctive VOC, which has been identified as 2-pentanone. This proof-of-principle study shows the potential of our high-resolution GC-IMS in the clinical environment. Due to different linear dynamic response ranges, the data of GC-IMS and GC-APCI-MS were only comparable to a limited extent.

A dual center study to compare breath volatile organic compounds from smokers and non-smokers with and without COPD.

There is increasing evidence that breath volatile organic compounds (VOC) have the potential to support the diagnosis and management of inflammatory diseases such as COPD. In this study we used a novel breath sampling device to search for COPD related VOCs. We included a large number of healthy controls and patients with mild to moderate COPD, recruited subjects at two different sites and carefully controlled for smoking. 222 subjects were recruited in Hannover and Marburg, and inhaled cleaned room air before exhaling into a stainless steel reservoir under exhalation flow control. Breath samples (2.5 l) were continuously drawn onto two Tenax(®) TA adsorption tubes and analyzed in Hannover using thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). Data of 134 identified VOCs from 190 subjects (52 healthy non-smokers, 52 COPD ex-smokers, 49 healthy smokers, 37 smokers with COPD) were included into the analysis. Active smokers could be clearly discriminated by higher values for combustion products and smoking related VOCs correlated with exhaled carbon monoxide (CO), indicating the validity of our data. Subjects from the study sites could be discriminated even after exclusion of cleaning related VOCs. Linear discriminant analysis correctly classified 89.4% of COPD patients in the non/ex-smoking group (cross validation (CV): 85.6%), and 82.6% of COPD patients in the actively smoking group (CV: 77.9%). We extensively characterized 134 breath VOCs and provide evidence for 14 COPD related VOCs of which 10 have not been reported before. Our results show that, for the utilization of breath VOCs for diagnosis and disease management of COPD, not only the known effects of smoking but also site specific differences need to be considered. We detected novel COPD related breath VOCs that now need to be tested in longitudinal studies for reproducibility, response to treatment and changes in disease severity.

Reduced per- and postoperative mortality following the use of urea during elective cardiopulmonary bypass. A proposed treatment for the prevention of reduced red cell deformability during open heart surgery.

The vital micro-rheological function of the red cells to deform was monitored during extracorporeal circulation in 75 patients undergoing open heart surgery. Red cell deformability was assessed in vitro by estimating red cell filtration rate (RFR). Urea was given to 32 patients during surgery and the remaining 43 acted as controls. After one hour on cardiopulmonary bypass (CPB) all patients showed a significant reduction of red cell filtration rate which continually worsened. In control patients where the RFR was severely altered there appeared to be more morbidity and mortality (11.6%). Using this simple method it is possible for the perfusionist to assess blood damage rapidly and possibly anticipate a difficult postoperative recovery. Urea administered during CPB reduced the decrease in RFR by a significant extent and in these patients the postoperative course was relatively uneventful and all survived.

Brain temperature in volunteers subjected to intranasal cooling.

PURPOSE: Intranasal cooling can be used to initiate therapeutic hypothermia. However, direct measurement of brain temperature is difficult and the intra-cerebral distribution of temperature changes with cooling is unknown. The purpose of this study was to measure the brain temperature of human volunteers subjected to intranasal cooling using non-invasive magnetic resonance (MR) methods. METHODS: Intranasal balloons catheters circulated with saline at 20°C were applied for 60 min in ten awake volunteers. No sedation was used. Brain temperature changes were measured and mapped using MR spectroscopic imaging (MRSI) and phase-mapping techniques. Heart rate and blood pressure were monitored throughout the experiment. Rectal temperature was measured before and after the cooling. Mini Mental State Examination (MMSE) test and nasal inspection were done before and after the cooling. Questionnaires about the subjects' personal experience were completed after the experiment. RESULTS: Brain temperature decrease measured by MRSI was -1.7 ± 0.8°C and by phase-mapping -1.8 ± 0.9°C (n = 9) at the end of cooling. Spatial distribution of temperature changes was relatively uniform. Rectal temperature decreased by -0.5 ± 0.3°C (n = 5). The physiological parameters were stable and no shivering was reported. The volunteers remained alert during cooling and no cognitive dysfunctions were apparent in the MMSE test. Postcooling nasal examination detected increased nasal secretion in nine of the ten volunteers. Volunteers' acceptance of the method was good. CONCLUSION: Both MR techniques revealed brain temperature reductions after 60 min of intranasal cooling with balloons circulated with saline at 20°C in awake, unsedated volunteers.

The effect of urea on red cell deformability during cardiopulmonary bypass.

Red cell deformability was measured from the red cell filtration rate (RFR) in 33 patients undergoing cardiopulmonary bypass (CPB). Urea (1.0 g/kg b.w.) was given to 14 of the patients and 19 were controls in a prospective, blind study. The mean RFR (microliters/s) fell during 120 min of CPB, from 36.8 to 11.2 in the control group and from 37.4 to 25.0 in the urea group. In 17 patients undergoing single valve replacement, the mean RFR at CPB time 120 min had fallen from 38.5 to 17.4 in the controls and from 38.0 to 30.0 in the urea group. The corresponding figures in the 16 patients who underwent coronary bypass graft procedures were 35.0 to 3.5 (controls) and 36.8 to 20.8 (urea). The study confirmed the deleterious effect of CPB on the red cell and showed that this damage can be significantly reduced by administration of urea.

Evaluation of red cell damage during cardiopulmonary bypass.

In patients undergoing cardiopulmonary bypass (CPB), red cell damage was assessed by simultaneous measurement of of plasma-haemoglobin (P-Hb) and red cell filtration rate (RFR) (1). RFR was significantly reduced after 120 min as compared with 30 min (17.4 +/- 4.1 vs. 30.4 +/- 2.9 microliters/s). P-Hb, by contrast, was significantly higher at 60 min than at 30 min after start of CPB (195 +/- 27.2 vs. 73.8 +/- 8.1 microliters/s). Significant negative correlation was found between RFR and P-Hb (r = 0.68). Red cell deformability thus permitted qualitative assessment of red cell trauma during CPB and thereby an estimation of the rheologic disturbance caused to these cells by CPB during open-heart surgery.

Association between arrhythmias and reduced red cell deformability following cardiopulmonary bypass.

In 56 patients undergoing open-heart surgery, trauma to the red cells (reduced deformability) during cardiopulmonary bypass (CPB) was monitored by estimating reduction in red cell filtration rate (RFR). Treatment-requiring arrhythmias (atrial tachyarrhythmia and ventricular tachycardia) appearing more than 24 hours postoperatively were associated with RFR reduction after CPB. The incidence of arrhythmia was 31% in the patients with less than 25% fall in RFR, 53% in those with greater than 25% fall and 81% when the RFR reduction was greater than 75%. RFR fall preceded appearance of arrhythmia.

Changes in red cell deformability associated with anaesthesia and cardiopulmonary bypass in open-heart surgery.

Red cell deformability was observed during open-heart surgery in 59 patients. Deformability, assessed with a standard microfiltration method, was expressed as red cell filtration rate (RFR) in microliter/s. The mean preoperative value, 38.9 +/- 1.0 microliter/s, showed a generally falling tendency. The first significant decrease in mean RFR (by 18%) followed induction of general anaesthesia, and the second (by 15%) was seen 60 min after the start of cardiopulmonary bypass (CPB). The major decrease in RFR during CPB was found at the end of bypass, when it was reduced to 62% of the pre-CPB value. The percentage RFR reduction at the end of CPB showed significant correlation with 1) CPB duration (r = 0.49), 2) oxygen flow rate index (OFRI), i.e. flow/min in the bubble oxygenator/m2 bsa (r = 0.38), and 3) blood flow rate index (BFRI), i.e. average volume of blood pumped through the heart-lung machine/min CPB time/m2 bsa (r = 0.51).

Association between bleeding and reduced red cell deformability following cardiopulmonary bypass.

In 56 patients undergoing open-heart surgery, red cell trauma during and following cardiopulmonary bypass (CPB) was monitored with a microfiltration method that estimated deformability of the cells. Red cell deformability was reduced by 38% during CPB and at a slower rate thereafter. The lowest filterability rate was reached on the second day, after which improvement began. In patients who had undergone coronary artery bypass grafting, preoperative values of red cell deformability were reached after 6 weeks. Following valve replacement, however, preoperative values were not regained during this period, which was attributed to continuous mechanical trauma by the artificial valves. A 50% reduction of red cell filterability from the end of CPB to 12 and 24 hours from the start of CPB was associated with heavy blood loss (greater than 1,000 ml) from drains. Reduced red cell deformability thus showed relationship with a bleeding tendency following use of CPB.

Association between pulmonary dysfunction and reduced red cell deformability following cardiopulmonary bypass.

Fifty-six patients undergoing open-heart surgery were monitored for red cell trauma during cardiopulmonary bypass (CPB), using a standard red cell microfiltration method. The average red cell deformability was reduced by 38%. Respirator time was shorter in the patients with lesser degrees of red cell trauma, and vice versa. After extubation, the tendency to hypercapnia was greatest in the patients with most red cell trauma during CPB. Hypoxic tendencies in the first 24 postextubation hours were comparably distributed among all levels of red cell trauma.