Laser speckle contrast imaging for intraoperative assessment of intestinal microcirculation in normo- and hypovolemic circulation in a porcine model.

INTRODUCTION: Healing is essential for successful colorectal surgery. Optimal microcirculation is needed to ensure this; however, this is only subjectively assessed by the surgeon. Laser Speckle Contrast Imaging (LSCI) is an objective non-contact, image-based method to quantify microcirculation in bowel ends. This study aimed to evaluate the application of LSCI in an open surgery porcine model, determine differences between normal and impaired microcirculation, and test the LSCI applicability to repeated measurements. METHOD: A midline laparotomy was made in ten healthy female pigs to expose the colon and small intestine. Subsequently, baseline measurements were conducted. A local arteria supplying the colonic or small intestine mesentery was clamped for 5 min. and LSCI measures were made again. After an hour's rest, LSCI measurements were done in two unaffected areas on the colon and the small intestine, and baseline values were recorded. Hypotension was induced with rapid bleeding and LSCI measurements were done. After the mean arterial blood pressure (MAP) dropped to 50-60 mmHg, norepinephrine infusion was started. At a stable MAP of 85-100 mmHg, LSCI measurements were repeated at 0 min. and 30 min. during continuous norepinephrine infusion. RESULTS: Cross-clamping caused LSCI levels to drop equally in both the colon and small intestine by 60% in the entire the clamped zone. Compared to baseline, the microcirculation measured by LSCI in the unclamped adjacent transition zone was diminished by 33% and 40%, colon and small intestines, respectively. During hypotension due to bleeding, LSCI decreased as expected. When MAP was stabilized by norepinephrine infusion, LSCI values dropped further: compared to baseline, measurements decreased with 24% and 20% in colon and small intestines, respectively. CONCLUSION: LSCI can be used as a quantitative, real-time, non-contact method to detect changes in the microcirculation during open intestinal surgery with large changes in microcirculation due to e.g., hypovolemic and norepinephrine infusion. It is simple to use and in contrast to the existing intraoperative microcirculation assessment techniques, LSCI stands out primarily for its elimination of the requirement for a dye. As our study has shown, this feature allows us to perform time-independent measurements and repeat them indefinitely in nearby regions without compromising the effectiveness of the method.

Effects of glepaglutide, a long-acting glucagon-like peptide-2 analog, on intestinal morphology and perfusion in patients with short bowel syndrome: Findings from a randomized phase 2 trial.

BACKGROUND: The proadaptive effects of glucagon-like peptide-2 (GLP-2) include stimulation of intestinal mucosal growth as well as intestinal blood flow and angiogenesis. We have recently reported that daily subcutaneous injections of glepaglutide, a long-acting GLP-2 analog, improved intestinal absorptive function in patients with short bowel syndrome (SBS). As secondary and exploratory end points, the effects of glepaglutide on intestinal morphology and perfusion are reported. METHODS: The following assessments were done in 18 patients with SBS in a randomized, crossover, dose-finding, phase 2 trial before and after three weeks of treatment with glepaglutide: plasma citrulline and mucosa biopsies to assess changes in (1) intestinal morphology by immunohistochemistry and (2) gene expressions associated with absorption, proliferation, and markers of tight-junction integrity by quantitative polymerase chain reaction. Intestinal perfusion was assessed in stoma nipples by laser speckle contrast imaging and quantitative fluorescence angiography with indocyanine green. RESULTS: In the 1- and 10-mg dose groups, glepaglutide significantly increased plasma citrulline by 15.3 µmol/L (P = 0.001) and 15.6 µmol/L (P = 0.001), respectively. Trends toward an increase in villus height, crypt depth, and epithelium height were seen in the same groups. No significant changes were seen in gene expressions or intestinal perfusion. CONCLUSION: The increase in plasma citrulline and the morphological improvements may partly account for improvement in the intestinal absorptive function. However, the finding of a stability in perfusion after three weeks of treatment with glepaglutide may have been preceded by a more profound acute-phase increase in intestinal perfusion at treatment initiation.

Mid-regional plasma pro-atrial natriuretic peptide and stroke volume responsiveness for detecting deviations in central blood volume following major abdominal surgery.

BACKGROUND: A reduced central blood volume is reflected by a decrease in mid-regional plasma pro-atrial natriuretic peptide (MR-proANP), a stable precursor of ANP, and a volume deficit may also be assessed by the stroke volume (SV) response to head-down tilt (HDT). We determined plasma MR-proANP during major abdominal procedures and evaluated whether the patients were volume responsive by the end of the surgery, taking the fluid balance and the crystalloid/colloid ratio into account. METHODS: Patients undergoing pancreatic (n = 25), liver (n = 25), or gastroesophageal (n = 38) surgery were included prospectively. Plasma MR-proANP was determined before and after surgery, and the fluid response was assessed by the SV response to 10° HDT after the procedure. The fluid strategy was based mainly on lactated Ringer's solution for gastroesophageal procedures, while for pancreas and liver surgery, more human albumin 5% was administered. RESULTS: Plasma MR-proANP decreased for patients undergoing gastroesophageal surgery (-9% [95% CI -3.2 to -15.3], p = .004) and 10 patients were fluid responsive by the end of surgery (∆SV > 10% during HDT) with an administered crystalloid/colloid ratio of 3.3 (fluid balance +1389 ± 452 ml). Furthermore, plasma MR-proANP and fluid balance were correlated (r = .352 [95% CI 0.031-0.674], p < .001). In contrast, plasma MR-proANP did not change significantly during pancreatic and liver surgery during which the crystalloid/colloid ratio was 1.0 (fluid balance +385 ± 478 ml) and 1.9 (fluid balance +513 ± 381 ml), respectively. For these patients, there was no correlation between plasma MR-proANP and fluid balance, and no patient was fluid responsive. CONCLUSION: Plasma MR-proANP was reduced in fluid responsive patients by the end of surgery for the patients for whom the fluid strategy was based on more lactated Ringer's solution than human albumin 5%.

Mesenteric traction syndrome in pigs: A single-blinded, randomized controlled trial.

Background: Mesenteric traction syndrome is commonly observed in patients undergoing upper abdominal surgery and is associated with severe postoperative complications. A triad of hypotension, tachycardia, and facial flushing seems provoked by prostacyclin (PGI2) release from the gut in response to mesenteric traction. The administration of nonsteroidal anti-inflammatory drugs (NSAID) inhibits PGI2 release, stabilizing the hemodynamic response. Here, we examined the effect of mesenteric traction on splanchnic blood flow in pigs randomized to NSAID or placebo treatment. Materials and Methods: Twenty pigs were allocated to either ketorolac or placebo treatment. Five minutes of manual mesenteric traction was applied. Plasma 6-keto-PGF1α, a stable metabolite of PGI2, hemodynamic variables, and regional blood flow (laser speckle contrast imaging) to the liver, stomach, small intestine, upper lip, and snout (laser Doppler flowmetry) were recorded prior to traction and 5 and 30 minutes thereafter. Results: Both groups of pigs presented a decrease in systemic vascular resistance (P = .01), mean arterial blood pressure (P = .001), and blood flow in the gastric antrum (P = .002). Plasma 6-keto-PGF1α did not increase in either group (P = .195), and cardiac output, heart rate, central venous pressure, and blood flow to the liver, small intestine, upper lip, and snout remained unchanged. Conclusion: Mesenteric traction resulted in cardiovascular depression, including reduced blood flow in the gastric antrum. Plasma 6-keto-PGF1α did not increase, and ketorolac administration did not alter the response to mesenteric traction. Furthers studies are needed to identify which substance is responsible for eliciting the cardiovascular response to mesenteric traction in pigs.

Hypotension Associated with MTS is Aggravated by Early Activation of TEA During Open Esophagectomy.

OBJECTIVE: A mesenteric traction syndrome (MTS) is elicited by prostacyclin (PGI2)-induced vasodilation and identified by facial flushing, tachycardia, and hypotension during abdominal surgery. We evaluated whether thoracic epidural anesthesia (TEA) influences the incidence of MTS. DESIGN: Randomized, blinded controlled trial. SETTING: Single-center university hospital. PARTICIPANTS: Fifty patients undergoing open esophagectomy. INTERVENTIONS: Patients were randomized to either early (EA, after induction of general anesthesia) or late activation of TEA (LA, after re-established gastric continuity). Plasma 6-keto-PGF1α, a stable metabolite of PGI2 and interleukine-6 (IL6) were measured in plasma during surgery along with hemodynamic variables and MTS graded according to facial flushing together with plasma C-reactive protein on the third post-operative day. RESULTS: Forty-five patients met the inclusion criteria. Development of MTS tended to be more prevalent with EA (n=13/25 [52%]) than with LA TEA (n=5/20 [25%], p=0.08). For patients who developed MTS, there was a transient increase in plasma 6-keto-PGF1α by 15 min of surgery and plasma IL6 (p<0.001) as C-reactive protein (P<0.009) increased. EA TEA influenced the amount of phenylephrine needed to maintain mean arterial pressure >60 mmHg in patients who developed MTS (0.16 [0.016-0.019] mg/min vs MTS and LA TEA 0.000 [0.000-0.005] mg/min, p<0.001). CONCLUSION: The incidence of MTS is not prevented by TEA in patients undergoing open esophagectomy. On the contrary, the risk of hypotension is increased in patients exposed to TEA during surgery, and the results suggest that it is advantageous to delay activation of TEA. Also, MTS seems to be associated with a systemic inflammatory response, maybe explaining the aggravated post-operative outcome.

The Incidence of Free Peritoneal Tumor Cells before and after Neoadjuvant Chemotherapy in Gastroesophageal Junction Cancer.

CONTEXT: The utility of peritoneal washing cytology in patients with gastroesophageal junction cancer has not been thoroughly evaluated. AIMS: The study aimed to determine the incidence of free peritoneal tumor cells by peritoneal washing cytology before and after neoadjuvant chemotherapy using conventional cytopathological methods and immunohistochemical staining for the analysis of peritoneal washings. SETTINGS AND DESIGN: A prospective study conducted at a single tertiary referral hospital. MATERIALS AND METHODS: Patients with gastroesophageal junction cancer and without suspicion of intra- or extraabdominal metastases before the staging laparoscopy were prospectively and consecutively enrolled. Peritoneal washing cytology was performed at staging laparoscopy (primary cytology) and after neoadjuvant chemotherapy during robot-assisted or open resection (secondary cytology). Peritoneal fluid samples were analyzed by conventional cytology and an immunohistochemical panel. RESULTS: Overall, 81 patients met the primary inclusion criteria. During primary cytology, positive cytology without overt metastases (C1M0) was detected in three patients (3.8%) while five patients (6.3%) had overt intra-abdominal metastases but negative cytology (C0M1). None of the patients with C1M0 underwent surgery due to extra-abdominal (n = 1) or intra-abdominal metastases (n = 2), and the overall survival was 4, 7, and 14 months. During secondary cytology, no patients with free peritoneal tumor cells were identified, but seven patients were classified as C0M1 (10.9%). CONCLUSIONS: The incidence of C1M0 was 3.8% and 0% before and after neoadjuvant chemotherapy, respectively in patients with gastroesophageal junction cancer. Free peritoneal tumor cells were not identified in several patients with intra-abdominal metastases suggesting that peritoneal washing cytology with conventional cytology and immunohistochemical staining lack sensitivity.

Development of a severe mesenteric traction syndrome during major abdominal surgery is associated with increased postoperative morbidity: Secondary data analysis on prospective cohorts.

PURPOSE: MTS is elicited during open abdominal surgery and is characterized by facial flushing, hypotension, and tachycardia in response to the release of prostacyclin (PGI2) to plasma. MTS seems to affect postoperative morbidity, but data from larger cohorts are lacking. We aimed to determine the impact of severe mesenteric traction syndrome (MTS) on postoperative morbidity in patients undergoing open upper gastrointestinal surgery. METHODS: The study was a secondary analysis of data from three cohorts (n = 137). The patients were graded for severity of MTS intraoperatively, and hemodynamic variables and blood samples for plasma 6-keto-PGF1α, a stable metabolite of PGI2, were obtained at defined time points. Postoperative morbidity was evaluated by the comprehensive complication index (CCI) and the Dindo-Clavien classification (DC). RESULTS: Patients undergoing either esophagectomy (n = 70), gastrectomy (n = 22), liver- (n = 23), or pancreatic resection (n = 22) were included. Severe MTS was significantly associated with increased postoperative morbidity, i.e., CCI ≥ 26.2 (OR 3.06 [95% CI 1.1-6.6]; p = 0.03) and risk of severe complications, i.e., DC ≥3b (OR 3.1 [95% CI 1.2-8.2]; p = 0.023). Furthermore, patients with severe MTS had increased length of stay (OR 10.1 [95% CI 1.9-54.3]; p = 0.007) and were more likely to be admitted to the intensive care unit (OR = 7.3 [95% CI 1.3-41.9]; p = 0.027), but there was no difference in 1-year mortality. CONCLUSION: Occurrence of severe MTS during upper gastrointestinal surgery is associated with increased postoperative morbidity as indicated by an increased rate of severe complications, length of stay, and admission to the ICU. It remains to be determined whether inhibition of MTS enhances postoperative recovery.

Effect of hypotensive hypovolemia and thoracic epidural anesthesia on plasma pro-atrial natriuretic peptide to indicate deviations in central blood volume in pigs: a blinded, randomized controlled trial.

PURPOSE: Changes in plasma pro-atrial natriuretic peptide (proANP) may indicate deviations in the central blood volume (CBV). We evaluated the plasma proANP response to hypotensive hypovolemia under the influence of thoracic epidural anesthesia (TEA) in pigs. We hypothesized that plasma proANP would decrease in response to hypotensive hypovolemia and that TEA would aggravate the proANP response, reflecting a further decrease in CBV. DESIGN: Randomized, blinded, controlled trial. SETTING: A university-affiliated experimental facility. PARTICIPANTS: Twenty pigs randomized to administration of saline (placebo) or bupivacaine with morphine (TEA) in the epidural space at Th8-Th10. INTERVENTIONS: Relative hypovolemia was established by an inflatable Foley catheter positioned in the inferior caval vein just below the heart (caval obstruction), and hemorrhage-induced hypovolemia was by withdrawal of blood from the femoral artery, both aiming at a mean arterial pressure (MAP) of 50-60 mmHg. Hemodynamic variables and plasma proANP were determined before and after the interventions. RESULTS: Caval obstruction and withdrawal of blood reduced MAP to 50-60 mmHg. Accordingly, cardiac output, central venous pressure, and mixed venous oxygen saturation decreased (p<0.05). Yet, plasma proANP was stable after both caval obstruction (TEA: 72 [63-78] to 80 pmol/L [72-85], p=0.09 and placebo: 64 [58-76] to 69 pmol/L [57-81], p=0.06) and withdrawal of blood (TEA: 74 [73-83] to 79 pmol/L [77-87], p=0.07 and placebo: 64 [56-77] to 67 pmol/L [58-78], p=0.15). CONCLUSION: Plasma proANP was stable in response to relative and hemorrhage-induced hypovolemia to a MAP of 50-60 mmHg, and the response was independent of TEA. The findings suggest that alterations in plasma proANP do not follow deviations in CBV during hypotensive hypovolemia in pigs.

Effects of glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, on markers of liver status in patients with short bowel syndrome: findings from a randomised phase 2 trial.

BACKGROUND: With the introduction of glucagon-like peptide-2 (GLP-2) in the treatment of short bowel syndrome (SBS), there is emerging evidence that GLP-2 may play a role in the restoration of the disturbed homeostatic feedback in the gut-liver axis and may ameliorate SBS-associated liver damage. We have previously presented that daily subcutaneous injections with 1 and 10 mg of glepaglutide improved intestinal function in patients with SBS. As exploratory endpoints, we here assessed the effect of glepaglutide on liver function. METHODS: Liver tests, transient elastography (TE) with controlled attenuation parameter (CAP), indocyanine green (ICG) kinetics, soluble CD163 (sCD163), soluble mannose receptor (sMR), and lipopolysaccharide binding protein (LBP) were assessed in 18 patients with SBS in a randomised, cross-over, dose-finding phase 2 trial before and after three weeks of treatment with glepaglutide. This trial is completed and registered at ClinicalTrials.gov: NCT02690025. FINDINGS: Between Feb 2016 and Jan 2017, 22 patients with SBS were screened. Of these, 18 patients were randomised and treated with glepaglutide; 16 patients completed the trial. Treatment with glepaglutide was associated with increase in TE and ICG-elimination. In the 10 mg dose group, glepaglutide increased sCD163 by 0·44 mg/mL (P = 0·0498), and alkaline phosphatase (ALP) decreased in the 1 mg dose group by 33 U/L (P = 0·032). CAP, sMR, LBP, liver transaminases, and INR were not affected. INTERPRETATION: Glepaglutide may improve hepatic excretory function, but at the same time activate resident liver macrophages and increase liver stiffness. The excretory and the stiffness findings may to some extent relate to increased splanchnic blood flow which would not influence the marker of macrophage activation. Thus, glepaglutide exerted diverse effects on liver status that call for attention in future studies. FUNDING: Zealand Pharma.

Laser speckle contrast imaging and quantitative fluorescence angiography for perfusion assessment.

PURPOSE: Indocyanine green fluorescence angiography (ICG-FA) is an established technique for assessment of intestinal perfusion during gastrointestinal surgery, whereas quantitative ICG-FA (q-ICG) and laser speckle contrast imaging (LSCI) are relatively unproven. The study aimed to investigate whether the techniques could be applied interchangeably for perfusion assessment. METHODS: Nineteen pigs underwent laparotomy, two minor resections of the small bowel, and anastomoses. Additionally, seven pigs had parts of their stomach and small intestine de-vascularized. Data was also collected from an in vivo model (inferior caval vein measurements in two additional pigs) and an ex vivo flow model, allowing for standardization of experimental flow, distance, and angulation. Q-ICG and LSCI were performed, so that regions of interest were matched between the two modalities in the analyses, ensuring coverage of the same tissue. RESULTS: The overall correlation of q-ICG and LSCI evaluated in the porcine model was modest (rho = 0.45, p < 0.001), but high in tissue with low perfusion (rho = 0.74, p < 0.001). Flux values obtained by LSCI from the ex vivo flow model revealed a decreasing flux with linearly increasing distance as well as angulation to the model. The Q-ICG perfusion values obtained varied slightly with increasing distance as well as angulation to the model. CONCLUSIONS: Q-ICG and LSCI cannot be used interchangeably but may supplement each other. LSCI is profoundly affected by angulation and distance. In comparison, q-ICG is minimally affected by changing experimental conditions and is more readily applicable in minimally invasive surgery.

Effect of early versus delayed activation of thoracic epidural anesthesia on plasma pro-atrial natriuretic peptide to indicate deviations in central blood volume during esophagectomy.

BACKGROUND AND OBJECTIVES: A side effect to thoracic epidural anesthesia (TEA) is hypotension induced by central hypovolemia. This study addressed whether early activation (EA) versus late activation (LA) of TEA affects plasma pro-atrial natriuretic peptide (proANP) reflecting deviations in the central blood volume (CBV). We hypothesized that EA TEA would reduce plasma proANP, thus reflecting a decrease in CBV. METHODS: A randomized, controlled, single-blinded trial was conducted. Patients undergoing open esophagectomy were randomized to EA (n=25, after induction of general anesthesia) or LA TEA (n=25, after re-established gastric continuity) with the epidural catheter placed at the interspaces Th7-8 or Th8-9. Plasma proANP was determined repetitively along with hemodynamic variables and administration of fluid/vasopressors as postoperative complications were noted. RESULTS: With EA TEA, plasma proANP decreased following induction of anesthesia to the end of surgery (13%; 113±68 to 99±49 pmol/L; p=0.026), but that was not the case in the LA group (3%; 97±44 to 94±49 pmol/L; p=0.565) despite equal fluid balance (+1584±582 vs +1560±563 mL; p=0.888). Accordingly, the EA group required excessive treatment with vasopressors to maintain MAP >60 mm Hg during surgery (2.7±2 vs 1.6±1.4 ephedrine boluses; p=0.033 and infusion of phenylephrine for 216±86 vs 58±91 min; p<0.001). Plasma proANP and fluid balance were correlated only for EA patients (r=0.44; 95% CI 0.04 to 0.91; p=0.033). CONCLUSIONS: EA TEA reduces plasma proANP indicating that CBV becomes affected. Based on a correlation between plasma proANP and fluid balance, a 2000 mL volume surplus of lactated Ringer's solution is required to maintain plasma proANP stable during open esophagectomy. TRIAL REGISTRATION NUMBER: 2014-002036-14 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-002036-14).

Glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, for patients with short bowel syndrome: a randomised phase 2 trial.

BACKGROUND: Patients with short bowel syndrome might have impaired postprandial endogenous glucagon-like peptide-2 (GLP-2) secretion, which is required for optimal intestinal adaptation. We aimed to assess the therapeutic potential of glepaglutide, a novel long-acting GLP-2 analogue, for reducing faecal output and increasing intestinal absorption in patients with short bowel syndrome. METHODS: In this single-centre, double-blind, crossover, randomised phase 2 trial, adults (aged ≥18 to ≤90 years) with short bowel syndrome and with a faecal wet weight output of 1500 g/day or more were randomly assigned to receive one of six dose sequences of glepaglutide (10 mg, 1 mg; 10 mg, 0·1 mg; 1 mg, 10 mg; 1 mg, 0·1 mg; 0·1 mg, 10 mg; or 0·1 mg, 1 mg). Patients received daily subcutaneous injections of the first assigned dose of glepaglutide for 3 weeks, followed by a washout period of 4-8 weeks, and then the second dose of glepaglutide for 3 weeks. An unmasked statistician generated the randomisation list, and the trial investigator enrolled patients and assigned them their patient numbers. Trial investigators, patients, and other care providers were masked throughout the trial. The primary endpoint was the absolute change from baseline in faecal wet weight output, measured separately over the two treatment periods. Metabolic balance studies were done before and after each treatment period to assess the primary endpoint. Per-protocol analysis was used to assess the efficacy. Safety analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT02690025, and has completed. FINDINGS: Of the 22 patients screened between Feb 5, 2016, and Jan 25, 2017, 18 patients were randomly assigned and treated with glepaglutide; 16 patients completed the trial. Treatment with 1 mg and 10 mg glepaglutide changed the adjusted mean faecal output by -592 g/day (95% CI -913 to -272; p=0·002) and -833 g/day (-1152 to -515; p=0·0002) from baseline, respectively. No changes were observed with 0·1 mg glepaglutide. Of the 18 patients who were randomly assigned to treatment, common treatment-related adverse events were stoma complications (13 [72%] patients), injection site reactions (11 [61%]), peripheral oedema (ten [56%]), nausea and abdominal pain (eight [44%] each), polyuria and fatigue (six [33%] each), abdominal distention, vomiting, and dizziness (five [28%] each); and cough and decreased appetite (four [22%] each). Related or possibly related serious adverse events were reported in two patients in the 0·1 mg dose group and two patients in the 10 mg dose group. These events included abdominal pain, stoma obstruction, catheter-related sepsis, and infection of unknown origin. No patients died during the trial. INTERPRETATION: Glepaglutide was well tolerated, and was associated with improved intestinal absorption in patients with short bowel syndrome with 1 mg and 10 mg glepaglutide, but not with 0·1 mg glepaglutide. Larger phase 3 clinical trials of longer durations have been initiated to fully assess the safety and efficacy of glepaglutide. FUNDING: Zealand Pharma.

The effect of glucagon-like peptide-1 and glucagon-like peptide-2 on microcirculation: A systematic review.

GLP-1 and GLP-2 are gut-derived hormones used in the treatment of diabetes type-2 and short bowel syndrome, respectively. GLP-1 attenuates insulin resistance and GLP-2 reduces enterocyte apoptosis and enhances crypt cell proliferation in the small intestine. In addition, both hormones have vasoactive effects and may be useful in situations with impaired microcirculation. The aim of this systematic review was to provide an overview of the potential effects of GLP-1 and GLP-2 on microcirculation. A systematic search was performed independently by two authors in the following databases: PubMed, EMBASE, Cochrane library, Scopus, and Web of Science. Of 1111 screened papers, 20 studies were included in this review: 16 studies in animals, three in humans, and one in humans and rats. The studies were few and heterogeneous and had a high risk of bias. However, it seems that GLP-1 regulates the pancreatic, skeletal, and cardiac muscle flow, indicating a role in the glucose homeostasis, while GLP-2 acts primarily in the regulation of the microcirculation of the mid-intestine. These findings may be useful in gastrointestinal surgery and in situations with impaired microcirculation of the gut.

Laser speckle contrast imaging for quantitative assessment of facial flushing during mesenteric traction syndrome in upper gastrointestinal surgery.

The mesenteric traction syndrome (MTS) is associated with prostacyclin (PGI2) facilitated systemic vasodilatation during surgery and is identified by facial flushing. We hypothesized that severe facial flushing would be related to the highest concentrations of plasma PGI2 and accordingly to the highest levels of skin blood flow measured by laser speckle contrast imaging (LSCI). Patients scheduled for major upper abdominal surgery were consecutively included. Within the first hour of the procedure, facial flushing was scored according to a standardized scale, and skin blood flow (LSPU) was continuously measured on the forehead and the cheeks by LSCI. Arterial blood samples for 6-keto-PGF1α (stable metabolite of PGI2) and hemodynamic variables were obtained at defined time points. Overall, 66 patients were included. After 15 min of surgery, patients with severe flushing demonstrated the highest plasma 6-keto-PGF1α concentration and the most significant decrease in systemic vascular resistance. Accordingly, the skin blood flow on the forehead (238 [201-372] to 562 LSPU [433-729]) and the cheeks (341 [239-355] to 624 LSPU [468-917]) increased and were significantly higher than for patients with moderate or no flushing (both, P = 0.04). A cut-off value for skin blood flow could be defined for both the cheeks and the forehead for patients with severe flushing vs. no flushing (425/456 LSPU, sensitivity 75/76% and specificity 80/85%). MTS is linked to an increase in facial skin blood flow during upper gastrointestinal surgery. By applying LSCI, it is possible to quantitatively register facial blood flow, and thereby provide an objective tool for intraoperative verification of MTS.

The influence of norepinephrine and phenylephrine on cerebral perfusion and oxygenation during propofol-remifentanil and propofol-remifentanil-dexmedetomidine anaesthesia in piglets.

BACKGROUND: Vasopressors are frequently used to increase blood pressure in order to ensure sufficient cerebral perfusion and oxygenation (CPO) during hypotensive periods in anaesthetized patients. Efficacy depends both on the vasopressor and anaesthetic protocol used. Propofol-remifentanil total intravenous anaesthesia (TIVA) is common in human anaesthesia, and dexmedetomidine is increasingly used as adjuvant to facilitate better haemodynamic stability and analgesia. Little is known of its interaction with vasopressors and subsequent effects on CPO. This study investigates the CPO response to infusions of norepinephrine and phenylephrine in piglets during propofol-remifentanil and propofol-remifentanil-dexmedetomidine anaesthesia. Sixteen healthy female piglets (25-34 kg) were randomly allocated into a two-arm parallel group design with either normal blood pressure (NBP) or induced low blood pressure (LBP). Anaesthesia was induced with propofol without premedication and maintained with propofol-remifentanil TIVA, and finally supplemented with continuous infusion of dexmedetomidine. Norepinephrine and phenylephrine were infused in consecutive intervention periods before and after addition of dexmedetomidine. Cerebral perfusion measured by laser speckle contrast imaging was related to cerebral oxygenation as measured by an intracerebral Licox probe (partial pressure of oxygen) and transcranial near infrared spectroscopy technology (NIRS) (cerebral oxygen saturation). RESULTS: During propofol-remifentanil anaesthesia, increases in blood pressure by norepinephrine and phenylephrine did not change cerebral perfusion significantly, but cerebral partial pressure of oxygen (Licox) increased following vasopressors in both groups and increases following norepinephrine were significant (NBP: P = 0.04, LBP: P = 0.02). In contrast, cerebral oxygen saturation (NIRS) fell significantly in NBP following phenylephrine (P = 0.003), and following both norepinephrine (P = 0.02) and phenylephrine (P = 0.002) in LBP. Blood pressure increase by both norepinephrine and phenylephrine during propofol-remifentanil-dexmedetomidine anaesthesia was not followed by significant changes in cerebral perfusion. Licox measures increased significantly following both vasopressors in both groups, whereas the decreases in NIRS measures were only significant in the NBP group. CONCLUSIONS: Cerebral partial pressure of oxygen measured by Licox increased significantly in concert with the vasopressor induced increases in blood pressure in healthy piglets with both normal and low blood pressure. Cerebral oxygenation assessed by intracerebral Licox and transcranial NIRS showed opposing results to vasopressor infusions.

A mesenteric traction syndrome affects near-infrared spectroscopy evaluated cerebral oxygenation because skin blood flow increases.

During abdominal surgery manipulation of internal organs may induce a "mesenteric traction syndrome" (MTS) including a triad of flushing, hypotension, and tachycardia that lasts for about 30 min. We evaluated whether MTS affects near-infrared spectroscopy (NIRS) assessed frontal lobe oxygenation (ScO2) by an increase in forehead skin blood flow (SkBF). The study intended to include 10 patients who developed MTS during pancreaticoduodenectomy and 22 patients were enrolled (age 61 ± 8 years; mean ± SD). NIRS determined ScO2, laser Doppler flowmetry determined SkBF, cardiac output (CO) was evaluated by pulse-contour analysis (Modelflow), and transcranial Doppler assessed middle cerebral artery mean flow velocity (MCA Vmean). MTS was identified by flushing within 60 min after start of surgery. MTS developed 20 min (12-24; median with range) after the start of surgery and heart rate (78 ± 16 vs. 68 ± 17 bpm; P = 0.0032), CO (6.2 ± 1.4 vs. 5.3 ± 1.1 L min-1; P = 0.0086), SkBF (98 ± 35 vs. 80 ± 23 PU; P = 0.0271), and ScO2 (71 ± 6 vs. 67 ± 8%; P < 0.0001), but not MCA Vmean (32 ± 8 vs. 32 ± 7; P = 0.1881) were largest in the patients who developed MTS. In some patients undergoing abdominal surgery NIRS-determined ScO2 is at least temporarily affected by an increase in extra-cranial perfusion independent of cerebral blood flow as indicated by MCA Vmean. Thus, NIRS evaluation of ScO2 may overestimate cerebral oxygenation if patients flush during surgery.

Reproducibility and Reliability of Repeated Quantitative Fluorescence Angiography.

INTRODUCTION: When using fluorescence angiography (FA) in perioperative perfusion assessment, repeated measures with re-injections of fluorescent dye (ICG) may be required. However, repeated injections may cause saturation of dye in the tissue, exceeding the limit of fluorescence intensity that the camera can detect. As the emission of fluorescence is dependent of the excitatory light intensity, reduction of this may solve the problem. The aim of the present study was to investigate the reproducibility and reliability of repeated quantitative FA during a reduction of excitatory light.

Laser Speckle Contrast Imaging to Evaluate Bowel Lesions in Neonates with NEC.

Background Necrotizing enterocolitis (NEC) is the most frequent surgical emergency in newborns. Intestinal ischemia is considered a factor that precedes the development of NEC lesions. Laser speckle contrast imaging (LSCI) can be used to assess tissue microcirculation. We evaluated if LSCI may help to detect intestinal regions with reduced microcirculation in NEC. Case Report A male patient (gestational age, 26 [3/7] weeks; birth weight, 600 g) showed clinical signs of NEC 28 days after birth. X-ray revealed pneumatosis intestinalis and portal gas. Laparotomy showed NEC lesions with signs of transmural ischemia in the terminal ileum and cecum. Surgical resection lines (RLs) were marked, followed by LSCI measurements and resection of the bowel between the two RLs. Post hoc LSCI analyses were conducted on both sides of the proximal and distal RL. Low-flux values, indicating reduced microcirculation, were found in the macroscopically assessed necrotic bowel at the proximal RL, whereas higher flux values, indicating sufficient microcirculation, were found in the macroscopically assessed normal bowel. Discussion This study is the first description of intra-abdominal use of LSCI to evaluate tissue microcirculation in relation to NEC lesions. LSCI could be a valuable tool to distinguish between ischemic and nonischemic bowel in neonates undergoing surgery for NEC.

Evaluation of Gastric Microcirculation by Laser Speckle Contrast Imaging During Esophagectomy.

BACKGROUND: Thoracic epidural anesthesia (TEA) may provoke hypotension, and that, as well as the use of vasopressors and the surgical technique, could affect splanchnic microcirculation, in which the surgical target organ is of particular interest. This study used laser speckle contrast imaging (LSCI) to monitor gastric microcirculation during esophagectomy. STUDY DESIGN: Forty-five patients undergoing open esophagectomy were randomized to primary activation (EA; 25 patients) or no intraoperative activation (LA; 20 patients) of TEA. Phenylephrine managed intraoperative hypotension and gastric microcirculation was assessed at antrum and corpus area by LSCI. RESULTS: Antrum microcirculation (mean ± SD) was lower in the EA group at baseline (1,150 ± 189 laser speckle perfusion units [LSPU] vs LA group: 1,265 ± 163 LSPU; p = 0.036). In both groups, antrum microcirculation tended to decrease in response to anesthesia, TEA, and surgical procedure (LA: 1,265 ± 163 to 1,097 ± 184 LSPU, p = 0.021; EA: 1,150 ± 189 to 1,064 ± 177 LSPU, p = 0.093), with no difference between groups during the remaining laparotomy. Corpus microcirculation decreased in both groups from baseline to gastric pull-up in response to anesthesia, TEA, and surgery (LA: 1,081 ± 236 to 649 ± 165 LSPU, p < 0.001; EA: 1,011 ± 208 to 675 ± 178 LSPU, p < 0.001), but recovered after gastric continuity was re-established (EA to 795 ± 162 LSPU, p = 0.027; LA to 815 ± 166 LSPU, p = 0.014), with no significant differences between groups (p > 0.05). The EA group needed continued phenylephrine support to maintain blood pressure (216 ± 86 vs 58 ± 91 minutes; p < 0.001). CONCLUSIONS: During esophagectomy, gastric microcirculation can be followed in real-time by LSCI. Flow changes in the stomach seemed related more to surgery than to TEA/vasopressor support. Laser speckle contrast imaging could form basis for directing procedures to maintain the microcirculation.

The effect of dexmedetomidine on cerebral perfusion and oxygenation in healthy piglets with normal and lowered blood pressure anaesthetized with propofol-remifentanil total intravenous anaesthesia.

BACKGROUND: During anaesthesia and surgery, in particular neurosurgery, preservation of cerebral perfusion and oxygenation (CPO) is essential for normal postoperative brain function. The isolated effects on CPO of either individual anaesthetic drugs or entire anaesthetic protocols are of importance in both clinical and research settings. Total intravenous anaesthesia (TIVA) with propofol and remifentanil is widely used in human neuroanaesthesia. In addition, dexmedetomidine is receiving increasing attention as an anaesthetic adjuvant in neurosurgical, intensive care, and paediatric patients. Despite the extensive use of pigs as animal models in neuroscience and the increasing use of both propofol-remifentanil and dexmedetomidine, very little is known about their combined effect on CPO in pigs with uninjured brains. This study investigates the effect of dexmedetomidine on CPO in piglets with normal and lowered blood pressure during background anaesthesia with propofol-remifentanil TIVA. Sixteen healthy female Danish pigs (crossbreeds of Danish Landrace, Yorkshire and Duroc, 25-34 kg) were used. Three animals were subsequently excluded. The animals were randomly allocated into one of two groups with either normal blood pressure (NBP, n = 6) or with induced low blood pressure (LBP, n = 7). Both groups were subjected to the same experimental protocol. Intravenous propofol induction was performed without premedication. Anaesthesia was maintained with propofol-remifentanil TIVA, and later supplemented with continuous infusion of dexmedetomidine. Assessments of cerebral perfusion obtained by laser speckle contrast imaging (LSCI) were related to cerebral oxygenation measures (PbrO2) obtained by an intracerebral Clark-type Licox probe. RESULTS: Addition of dexmedetomidine resulted in a 32% reduction in median PbrO2 values for the LBP group (P = 0.03), but no significant changes in PbrO2 were observed for the NBP group. No significant changes in LSCI readings were observed in either group between any time points, despite a 28% decrease in the LBP group following dexmedetomidine administration. Caval block resulted in a significant (P = 0.02) reduction in median MAP from 68 mmHg (range 63-85) at PCB to 58 mmHg (range 53-63) in the LBP group, but no significant differences in either PbrO2 or LSCI were observed due to this intervention (P = 0.6 and P = 0.3 respectively). CONCLUSIONS: Addition of dexmedetomidine to propofol-remifentanil TIVA resulted in a significant decrease in cerebral oxygenation (PbrO2) measurements in piglets with lowered blood pressure. Cerebral perfusion (LSCI) did not decrease significantly in this group. In piglets with normal blood pressure, no significant changes in cerebral perfusion or oxygenation were seen in response to addition of dexmedetomidine to the background anaesthesia.