- Email: [email protected]
Real-Time Measurement of Rectal Mucosal Microcirculation During Cardiopulmonary Bypass
Real-Time Measurement of Rectal Mucosal Microcirculation During Cardiopulmonary Bypass Arndt-H. Kiessling, MD,* Christian Reyher, MD,† Michael Philipp, MD,* Andres Beiras-Fernandez, MD,* and Anton Moritz, MD* Objectives: Mesenteric ischemia is still a fatal event after cardiac procedures. No adequate intraoperative methods are available to monitor the gastrointestinal mucosal microcirculation in real-time conditions. The aim of the study was to assess a newly designed microprobe using laser Doppler flowmetry and remission spectroscopy. Design: One-group, prospective, nonrandomized, open, pilot diagnostic study. Setting: Monocenter university hospital. Participants: 50 patients (n ¼ 38 males, 67 ⫾ 6 years) scheduled for cardiopulmonary bypass (CPB) were prospectively included. Intervention: During anesthetic induction, the transrectal microprobe (30 15 mm) was positioned between the inferior and middle rectal valve (5-8 cm). Time periods were summarized at T1 ¼ pre-CPB, T2 ¼ CPB, T3 ¼ post–CPB. Measurements and Main Results: In 39 of 50 patients, data recruitment with the microprobe was successful.
Measurement failures were due to fecal contaminations and probe dislocations. Rectal blood flow and velocity significantly decreased after bypass initiation (T2). Lowest flow rates were recorded after cross-clamp removal and did not recover at the end of bypass (T3). No side effects of the probe were noted. Conclusions: The new microprobe allows reproducible, safe, intraoperative, real-time evaluation of the rectal mucosal microcirculation. It could be a useful diagnostic tool to prevent mesenteric ischemia by optimizing extracorporeal circulation in future studies. However, first correlation of rectal blood flow and postoperative events (eg, ischemia, lactate) in a large cohort are necessary. & 2014 Elsevier Inc. All rights reserved.
O
usually rapidly improves the situation. If selective angiography is not available, immediate laparotomy is indicated. Even with rapid intervention, a mortality of 50% is to be expected, and survival is unlikely after 12 hours.3 An intraoperative diagnostic method of real-time, direct measurement of intestinal mucosal blood flow would be desirable. The micro-lightguide spectrophotometer O2C (LEA Medizintechnik, Giessen, Germany) is a diagnostic tool for noninvasive determination of oxygen supply of tissues perfused with blood. The main measurement options using a glass fiber probe in the illuminated tissue are oxygen saturation of hemoglobin, relative hemoglobin quantity, relative blood flow, and blood flow velocity. The validity of the O2C device has been reported in numerous publications.4–7 Pathologic O2 supply, which can lead to angiogenesis or cell death with subsequent organ failure, can be assessed at an early stage by local measurement. Impairments of microcirculation of the mucosa can be evaluated objectively. With few exceptions, however, data were generated in the past by transdermal measurements. Only the further development of a rectal probe has now made an intraoperative measurement possible. The aim of this diagnostic pilot study was to obtain initial information regarding the reproducibility and practicability of the new method.
RGAN PERFUSION is difficult to monitor for diagnostic purposes during extracorporeal circulation in patients undergoing cardiac surgery. Surrogate parameters (eg, lactate) are used as diagnostic aids. Direct monitoring of functionality may be a challenge. The early postoperative phase is characterized by complications originating in the intraoperative, extracorporeal bypass time. These serious events in the intensive care setting include gastrointestinal tract complications, such as hemorrhage, ulceration, ileus, pancreatitis, peritonitis, intestinal ischemia, and mesenteric thrombosis. Ritz and Buhr showed that such complications are observed in 3% of cases.1 Of their patients, 25% required a laparotomy, indicating that the diagnosis of a gastrointestinal complication sometimes was made only by the surgeon or pathologist. A high mortality rate is associated with gastrointestinal (GI) complications.2 The most frequently described complication is gastrointestinal hemorrhage which, like most other gastrointestinal problems, is accessible to conservative or endoscopic therapy and has a comparatively favorable prognosis. Less common are ischemic events, which are associated with mortality rates between 70% and 100% and, therefore, represent a great challenge for cardiac surgical intensive care physicians.1 The main problem presented by intestinal ischemia is late diagnosis, usually because of nonspecific symptoms. Other organ complications are noticed sooner, because cardiac, pulmonary, and renal functions are accessible to direct monitoring. This is not the case with intestinal ischemia, although rapid diagnosis is particularly important in this context because lethality is significantly lower with early versus late surgical intervention.1 Intestinal ischemia is admittedly difficult to diagnose in patients under analgesic sedation. Since GI complications occurs late, every patient with rising lactate levels and persistent, therapy refractory metabolic acidosis, which usually is accompanied by leukocytosis and paralytic ileus, should be referred immediately for selective angiography of the mesenteric vessels. In cases involving nonocclusive mesenteric ischemia, local vasodilator therapy (eg, with papaverine) can be performed during the same session, which
KEY WORDS: cardiopulmonary bypass, microcirculation, laser Doppler flowmetry, mucosa, mesenteric ischemia
From the *Department of Thoracic and Cardiovascular Surgery; and the †Clinic of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt am Main, Germany. Address reprint requests to Arndt-H. Kiessling, Department of Thoracic and Cardiovascular Surgery, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany. E-mail: [email protected] © 2014 Elsevier Inc. All rights reserved. 1053-0770/2601-0001$36.00/0 http://dx.doi.org/10.1053/j.jvca.2014.07.003
Journal of Cardiothoracic and Vascular Anesthesia, Vol 29, No 1 (February), 2015: pp 89–94
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METHODS Fifty patients (n = 38 males, 67 ⫾ 6 years, n = 41 coronary artery bypass grafts, n = 9 valve procedures and/or combinations) fulfilled the inclusion criteria (age 418 years, planned cardiac surgery procedure with use of cardiopulmonary bypass) and nonexclusion criteria (stoma, hemorrhoidal nodes, rectal cancer disease) and were prepared for rectal probe placement after induction of anesthesia. The characteristics and concomitant diseases reflected the usual cardiac surgery patient profiles (Table 1). Laxative measures (enema) were performed on the day before surgery to reduce fecal contamination. The probe was covered with a protective sheath coated with a local analgesic (Xylocain 2%, AstraZeneca, Wedel, Germany) and placed at a depth of 5-10 cm in the rectal ampulla with the aid of an introducer rod under digital control. The correct position and signal transmission were checked by observing the biphasic curve pattern. After monitoring was initiated, general anesthesia was induced (0.3-1 mg/kg of sufentanil (Sufenta, Janssen-Cilag GmbH, Neuss, Germany), 1-2.5 mg/kg of propofol (Disoprivan, AstraZeneca GmbH, Wedel, Germany), and 0.6 mg/kg of rocuronium (Esmeron, Essex GmbH, Munich, Germany). For maintenance of general anesthesia, all patients received 1 to 2 vol% sevoflurane (Sevoran, Abbott, Wiesbaden, Germany) and intermittent boluses of sufentanil. Isotonic crystalloid (Sterofundin, B. Braun GmbH, Melsungen, Germany) was infused perioperatively based on institutional standards. The indication for red blood cell transfusion was a hemoglobin o7.5 mg/dL. The extracorporeal circuit included a membrane oxygenator (Quadrox oxygenator, Maquet Cardiopulmonary AG, Hirrlingen, Germany) and a roller pump system (HL20. Maquet Cardiopulmonary AG) equipped with a cardioplegia heat exchanger (Plegiox, Maquet Cardiopulmonary AG). The circuit was primed with 1,250 mL of crystalloid solution (Sterofundin, B. Braun Melsungen AG, Melsungen, Germany) according to institutional standards. Heparin (HeparinNatrium Braun, B.Braun Melsungen AG) was administered to maintain an activated coagulation time (ACT) greater than 400 seconds. During cardiopulmonary bypass (CPB), nonpulsatile flow was maintained at 2.6 to 3 L/min/m2, and mean arterial pressure (MAP) was maintained at 50 to 70 mmHg by the administration of norepinephrine (Arterenol, Sanofi-Aventis GmbH, Hoechst, Germany). Myocardial protection was achieved with cold blood cardioplegia (201C). Extracorporeal circulation was performed under mild hypothermia (321C). On completion of surgery, the patients were warmed and weaned from CPB.
Table 1. Patient (n ¼ 50) Demographic Characteristics, Intraoperative Data, and Postoperative Course Age, years Male NYHA class ZIII Elective surgery ASA class 42 LV function o30% Diabetes type II CPB (min)) CCT (min) Operation time (min) CABG In-hospital mortality 30-day mortality Redo-thoracotomy Mesenteric ischemia
67 ⫾ 6 38/50 19/50 50/50 11/50 2/50 31/50 120 ⫾ 48 min 73 ⫾ 41 min 244 ⫾ 54 min 41/50 2/50 2/40 4/50 0/50
Abbreviations: ASA, American Society of Anesthesiologists; CABG, coronary artery bypass graft; CCT, cross-clamp time; CPB, cardiopulmonary bypass; LV, left ventricle; NYHA, New York Heart Assocation.
To reverse the anticoagulant effects of heparin, protamine sulfate (Protaminsulfat, Novo Nordisk Pharma GmbH, Vienna, Austria) was administered, guided by the ACT.8 The optical method used for measuring relative blood flow by laser Doppler, hemoglobin amount, and hemoglobin oxygenation has been described in detail in the literature.11 In brief, the micro-light guide spectrophotometer O2C (Oxygen to See; LEA Medizintechnik, Giessen, Germany) transmits continuous laser light (830 nm and 30 mW) and white light (20 W, 500-800 nm, 1 nm resolution) to the tissue where it is scattered and collected at the surface (Fig 1). The collected light is split into its spectral components by a charge-coupled device array and is converted into an electrical signal. The laser Doppler shift is detected, and the product of moving erythrocytes and the time velocity of each erythrocyte are used to calculate the relative rectal blood flow (RBF). White light is used for the detection of oxygen saturation (SO2) and relative amount of hemoglobin (rHb). The tissue hemoglobin value is determined by the amount of light absorbed by the tissue. This measurement represents a hemoglobin concentration per tissue volume and is independent of vessel density, vessel lumen, and hemoglobin quantity in the blood.7 The change in color of the reflected light is due to wavelength-dependent absorption of the applied white light and can be used to calculate the oxygen saturation of hemoglobin. Adjustment of the distance between the application of the light and the detection of the reflected light allows detection in different tissues.8,9 In the present study, a newly developed transrectal probe (LFX 8, LEA Medizintechnik, Giessen, Germany) was placed before draping the patient in the operating room and was removed at the end of surgery. Rectal blood flow, rHb, and SO2 measurements were performed continuously (Fig 2). Interpretation of the measured results in the direct time interval was difficult. A high amplitude interval within the 1-second measurement cycles results in a large spread, which impedes an assessment of the measured values for SO2, rHb, flow, and velocity. Calculation of the arithmetic means of the measured values for 5-minute intervals greatly improves on-screen interpretation of the measured values (Fig 3). For statistical processing, the means of the time intervals t1 ¼ pre-pump, t2 ¼ cross-clamp, and t3 ¼ reperfusion were calculated for all 39 patients. The evaluation and graphical presentation of the recorded data were performed with tables and line charts using Excel 2010 (Microsoft Corporation, Redmond, WA) and the statistics program SPSS 21.0 (IBM, Chicago, IL), which also was used for the statistical analysis. The data sets were evaluated by calculating the mean and standard deviation of all data sets. Two sample dependent t tests for comparing means were used according to their function. An error probability of p o 0.05 was defined by consensus as statistically significant. No sample size calculation was performed for this one-arm diagnostic pilot study. Patients gave written informed consent (Clinical Trials Gov No.: NCT01425931 /Ethics Committee No.: 318/11). RESULTS
Because of patient disinfection, preparation for surgery, or fecal contamination, 11 patients experienced dislocation of the probe and loss of adequate signal strength. These were mainly coronary artery bypass graft procedures in which the legs were raised for disinfection before harvesting of venous bypass grafts. To avoid jeopardizing the sterility of the operative field, no repeat placement was attempted. None of the patients showed a proberelated complication. All of the patients had to be stabilized with vasopressors during perfusion to increase the MAP (norepinephrine, mean 0.08 μg/kg/min, range 0.05-0.5 μg/kg/min). No patient developed mesenteric ischemia or other gastrointestinal complications during the postoperative course. In-hospital mortality was 4%.
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Fig 1. The O2C device for the measurement of regional capillary venous rectal blood flow (rvRBF), oxygen saturation (srvO2), and hemoglobin concentration (rvHb); and the measurement principle of the O2C device is based on combined photospectrometry and laser Doppler flowmetry. Reprinted with the permission of LEA Medizintechnik GmbH, Giessen, Germany.
O2 saturation decreased on startup of CPB (68.14% ⫾ 19.9%) and also remained below baseline after opening the aortic clamp (65.07% ⫾ 16%). However, the values do not differ significantly (p ¼ 0.52). The fall both in SO2 and rHb possibly may be explained by hemodilution. The decrease is dependent on the duration of perfusion, but not on the start of CPB (Fig 4 and Table 2). The decrease in the relative Hb value also appeared to be hemodilution-related. The indication for transfusion during CPB was present at a critical Hb value of 7.5 mg/dL. The sensitivity of the O2C device was not sufficient to detect the administration of red blood cell concentrates with rectal measurement. Altogether, 5 of 39 patients received 1.2 units of red blood cells on average (range 1-3) during perfusion. The kinetics resemble
Fig 2. Novel rectal probe LFX8 designed to meet the special positioning requirements (special probe for stable measurements and anatomic design).
those of SO2 and flow: A decrease during perfusion and persistently low during the reperfusion phase without differing significantly from each other (Fig 4 and Table 2). The rectal microcirculation flow/velocity decreases with the duration of perfusion and reaches its lowest level before opening the aortic clamp. No significant differences were calculated (Fig 4 and Table 2). The microcirculation should be unimpaired by the hemodilution and can be interpreted as an effect of the perfusion. DISCUSSION
Laser Doppler Flowmetry (LDF) has been used to assess mucosal blood flow and a range of functions at different sites. Ohri et al studied the effect of CPB on the gastric mucosa of adults.9 They used a probe, positioned in the gut after retrograde insertion in a nasogastric tube. This enabled laser Doppler measurements to be taken with increased stability. Observations included profound reductions in mucosal blood flow during the hypothermic phase of CPB despite maintenance of MAP and flow. A close relationship between core temperature and gastric mucosal blood flow was found, and also between arterial pressure and gastric blood flow. Booker et al assessed the effect of CPB on neonatal gut mucosal blood flow at the rectum and investigated the effect of hypothermia/rewarming; it was found that neonates requiring aortic arch surgery may be at particular risk of gut mucosal hypoxia before and after surgery; with regard to temperature, laser doppler flowmetry (LDF) was reduced during cooling but was lowest during the rewarming phase.10,11 Emmanuel and Kamm12,13 found LDF to be highly reproducible and studied the effect on rectal mucosal blood flow of eating, smoking, body size, sex,
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Fig 3. Top: Raw data presentation with difficult visual interpretation of the time course with 1-second measurement points with high variability. Bottom: Plotting of means at 5-minute intervals improves visual interpretation of the measured results.
ovulatory status, and menstrual phase. Changes in mucosal blood flow induced by autonomically active drugs and nerve stimulation confirmed the role of the mucosal microcirculation as a measure of extrinsic nerve activity.12,13 Emmanuel et al,14 using LDF in a similar way, showed that patients with idiopathic constipation have impaired extrinsic gut nerve activity, particularly in those with slow transit. Hajivassiliou et al assessed blood flow distributions in the human colon during operations on 6 controls and 6 patients with inflammatory bowel disease undergoing colectomy; ischemia demarcation lines were identified before the onset of visible changes.15,16 But directly available monitoring of sufficient perfusion during extracorporeal circulation continues to be a major challenge.16 The monitoring of organ systems below skin level is especially a problem that, in many respects, has not been solved. In principle, laser Doppler, nailfold videomicroscopy, sidestream dark field imaging technique, SvO2, near-infrared spectroscopy, tonometry, sublingual capnometry, and microdialysis are available as possible bedside methods.17 However, none of these techniques allows intestinal diagnostic testing. A procedure already established outside rectal monitoring is lightguide tissue spectrophotometry with the instrument type
O2C. Clinical experience with O2C has been gathered in the following clinical fields: Arterial occlusive disease, wound healing disorders, inflammatory processes, compression control, amputation diagnostic testing, polyneuropathy, plastic surgery, and cardiac surgical applications for radial artery removal and mammary artery dissection.18,19 The design of a new probe made monitoring of the rectal microcirculation possible for the first time. The rationale of this pilot study was to evaluate the practicability and effectiveness of the new probe. Data were to be recorded continuously in 50 patients throughout the entire course of the operation. In 11 of 50 patients, fecal contamination or positional manipulations resulted in discontinuation of the measurement. The gravitational force of the probe head should be sufficient to retain the probe in position. Any type of assistive device that exerts additional pressure (eg, balloon catheter) on the probe head impairs the microcirculation and makes an assessment impossible. Firstly, therefore, sufficient preoperative bowel emptying should be ensured, and secondly, the patient’s passive movements during sterile washing should be executed only with great caution. The position of the probe remains to be discussed as a critical factor. The rectum has an anatomically different supply circulation compared with the rest of the large
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Fig 4. Mean and SD line of flow, rHb, velocity, and SO2 at the time points pre-pump, cross-clamp, and reperfusion. Increasing values after aortic cross-clamp without any recovery after removal and reperfusion.
intestine. For example, a large part of the rectum is supplied from the iliac artery and not from the inferior mesenteric artery, which is much more clinically relevant for intestinal ischemia. However, placing the probe intraluminally such that
the arterially-supplied area has changed is not possible under digital control. Endoscopic support would be necessary for this purpose but is ruled out as a routine measure because of its invasiveness.
Table 2. Overview of O2C Measured Values (SO2, rHb, flow, velocity) at 3 Different Time Points (Pre-pump, Cross-clamp, and Reperfusion) (n ¼ 39 Patients). Changes in Mean Among the 3 Time Points Were Not Significantly Different.
SO2 (%) Prepump Cross-clamp Reperfusion rHb (AU) Prepump Cross-clamp Reperfusion Flow (AU) Prepump Cross-clamp Reperfusion Velocity (AU) Prepump Cross-clamp Reperfusion
Mean
SD
Minimum
Maximum
Statistics
70.07 68.14 65.07
14.837 18.994 16.096
34 23 23
91 93 92
n.s.
42,10 39.38 35.79
10.510 12,031 10.594
22 15 18
64 62 68
n.s.
92,793 74.034 74.586
52,0227 37.6947 37.7014
20.0 6.0 16.0
280.0 195.0 190.0
n.s.
20.00 18.55 18.93
7.036 3.906 4.559
13 14 13
46 31 34
n.s.
Abbreviations: AU, arbitrary unit; n.s., not significant; rHb; sd, standard deviation.
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An alternative localization could be a buccal or sublingual measurement. Correlations between the sublingual microcirculation and mesenteric blood flow have been shown in intensive medical care studies in septic patients. The development of a buccal or sublingual probe possibly may offer advantages over rectal measurement. Advantages would include the possibility of correcting the position during an ongoing operation,
independence of the rectal evacuation status, and more substantial information about the intestinal blood flow. ACKNOWLEDGMENTS The authors thank Mrs. Sonja Friese (Study Coordinator, Goethe University Hospital, Frankfurt, Germany) for her assistance with the patient recruitment and data analysis.
REFERENCES 1. Ritz JP, Buhr HJ: Acute mesenteric ischemia [article in German]. Chirurg 82:863-866, 868-870, 2011 2. Markewitz A, Lante W: Organ failure in intensive care medicine for heart surgery. Dtsch Med Wochenschr 131:2485-2488, 2006 3. Boerma EC, Kaiferová K, Konijn AJ, et al: Rectal microcirculatory alterations after elective on-pump cardiac surgery. Minerva Anestesiol 77:698-703, 2011 4. Beckert S, Witte MB, Königsrainer A, Coerper S: The impact of the Micro-Lightguide O2C for the quantification of tissue ischemia in diabetic foot ulcers. Diabetes Care 27:2863-2867, 2004 5. Darmanin G, Jaggard M, Hettiaratchy S, et al: Evaluating optimal superficial limb perfusion at different angles using non-invasive microlightguide spectrophotometry. J Plast Reconstr Aesthet Surg 66: 821-826, 2013 6. Dragu A, Schnürer S, Horbach T, et al: Evaluation of intraoperative abdominal wall perfusion in post-bariatric abdominal dermolipectomy. Obes Facts 5:651-659, 2012 7. Klein KU, Schramm P, Glaser M, et al: Intraoperative monitoring of cerebral microcirculation and oxygenation—A feasibility study using a novel photo-spectrometric laser-Doppler flowmetry. J Neurosurg Anesthesiol 22:38-45, 2010 8. Weber CF, Jámbor C, Strasser C, et al: Normovolemic modified ultrafiltration is associated with better preserved platelet function and less postoperative blood loss in patients undergoing complex cardiac surgery: A randomized and controlled study. J Thorac Cardiovasc Surg 141:1298-1304, 2011 9. Ohri SK, Becket J, Brannan J, et al: Effects of cardiopulmonary bypass on gut blood flow, oxygen utilisation, and intramucosal pH. Ann Thorac Surg 57:1193-1199, 1994
10. Booker PD, Prosser DP, Franks R: Effect of hypothermia on rectal mucosal perfusion in infants undergoing cardiopulmonary bypass. Br J Anaesth 77:591-596, 1996a 11. Booker PD, Romer H, Franks R: Gut mucosal perfusion in neonates undergoing cardiopulmonary bypass. Br J Anaesth 77:597-602, 1996 12. Emmanuel AV, Kamm MA: Laser Doppler measurement of rectal mucosal blood flow. Gut 45:64-69, 1999 13. Emmanuel AV, Kamm MA: Laser Doppler flowmetry as a measure of extrinsic colonic innervation in functional bowel disease. Gut 46:212-217, 2000 14. Emmanuel AV, Mason HJ, Kamm MA: Relationship between psychological state and level of activity of extrinsic gut innervation in patients with a functional gut disorder. Gut 49:209-213, 2001 15. Hajivassiliou CA, Greer K, Fisher A, et al: Non-invasive measurement of colonic blood flow distribution using laser Doppler imaging. Br J Surg 85:52-55, 1998 16. Awan ZA, Wester T, Kvernebo K: Human microvascular imaging: A review of skin and tongue videomicroscopy techniques and analysing variables. Clin Physiol Funct Imaging 30:79-88, 2010 17. De Backer D, Ospina-Tascon G, Salgado D, et al: Monitoring the microcirculation in the critically ill patient: Current methods and future approaches. Intensive Care Med 36:1813-1825, 2010 18. Knobloch K, Lichtenberg A, Pichlmaier M, et al: Palmar microcirculation after harvesting of the radial artery in coronary revascularization. Ann Thorac Surg 79:1026-1030, discussion 1030, 2005 19. Knobloch K, Lichtenberg A, Pichlmaier M, et al: Microcirculation of the sternum following harvesting of the left internal mammary artery. Thorac Cardiovasc Surg 51:255-259, 2003
Measurement failures were due to fecal contaminations and probe dislocations. Rectal blood flow and velocity significantly decreased after bypass initiation (T2). Lowest flow rates were recorded after cross-clamp removal and did not recover at the end of bypass (T3). No side effects of the probe were noted. Conclusions: The new microprobe allows reproducible, safe, intraoperative, real-time evaluation of the rectal mucosal microcirculation. It could be a useful diagnostic tool to prevent mesenteric ischemia by optimizing extracorporeal circulation in future studies. However, first correlation of rectal blood flow and postoperative events (eg, ischemia, lactate) in a large cohort are necessary. & 2014 Elsevier Inc. All rights reserved.
O
usually rapidly improves the situation. If selective angiography is not available, immediate laparotomy is indicated. Even with rapid intervention, a mortality of 50% is to be expected, and survival is unlikely after 12 hours.3 An intraoperative diagnostic method of real-time, direct measurement of intestinal mucosal blood flow would be desirable. The micro-lightguide spectrophotometer O2C (LEA Medizintechnik, Giessen, Germany) is a diagnostic tool for noninvasive determination of oxygen supply of tissues perfused with blood. The main measurement options using a glass fiber probe in the illuminated tissue are oxygen saturation of hemoglobin, relative hemoglobin quantity, relative blood flow, and blood flow velocity. The validity of the O2C device has been reported in numerous publications.4–7 Pathologic O2 supply, which can lead to angiogenesis or cell death with subsequent organ failure, can be assessed at an early stage by local measurement. Impairments of microcirculation of the mucosa can be evaluated objectively. With few exceptions, however, data were generated in the past by transdermal measurements. Only the further development of a rectal probe has now made an intraoperative measurement possible. The aim of this diagnostic pilot study was to obtain initial information regarding the reproducibility and practicability of the new method.
RGAN PERFUSION is difficult to monitor for diagnostic purposes during extracorporeal circulation in patients undergoing cardiac surgery. Surrogate parameters (eg, lactate) are used as diagnostic aids. Direct monitoring of functionality may be a challenge. The early postoperative phase is characterized by complications originating in the intraoperative, extracorporeal bypass time. These serious events in the intensive care setting include gastrointestinal tract complications, such as hemorrhage, ulceration, ileus, pancreatitis, peritonitis, intestinal ischemia, and mesenteric thrombosis. Ritz and Buhr showed that such complications are observed in 3% of cases.1 Of their patients, 25% required a laparotomy, indicating that the diagnosis of a gastrointestinal complication sometimes was made only by the surgeon or pathologist. A high mortality rate is associated with gastrointestinal (GI) complications.2 The most frequently described complication is gastrointestinal hemorrhage which, like most other gastrointestinal problems, is accessible to conservative or endoscopic therapy and has a comparatively favorable prognosis. Less common are ischemic events, which are associated with mortality rates between 70% and 100% and, therefore, represent a great challenge for cardiac surgical intensive care physicians.1 The main problem presented by intestinal ischemia is late diagnosis, usually because of nonspecific symptoms. Other organ complications are noticed sooner, because cardiac, pulmonary, and renal functions are accessible to direct monitoring. This is not the case with intestinal ischemia, although rapid diagnosis is particularly important in this context because lethality is significantly lower with early versus late surgical intervention.1 Intestinal ischemia is admittedly difficult to diagnose in patients under analgesic sedation. Since GI complications occurs late, every patient with rising lactate levels and persistent, therapy refractory metabolic acidosis, which usually is accompanied by leukocytosis and paralytic ileus, should be referred immediately for selective angiography of the mesenteric vessels. In cases involving nonocclusive mesenteric ischemia, local vasodilator therapy (eg, with papaverine) can be performed during the same session, which
KEY WORDS: cardiopulmonary bypass, microcirculation, laser Doppler flowmetry, mucosa, mesenteric ischemia
From the *Department of Thoracic and Cardiovascular Surgery; and the †Clinic of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt am Main, Germany. Address reprint requests to Arndt-H. Kiessling, Department of Thoracic and Cardiovascular Surgery, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany. E-mail: [email protected] © 2014 Elsevier Inc. All rights reserved. 1053-0770/2601-0001$36.00/0 http://dx.doi.org/10.1053/j.jvca.2014.07.003
Journal of Cardiothoracic and Vascular Anesthesia, Vol 29, No 1 (February), 2015: pp 89–94
89
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KIESSLING ET AL
METHODS Fifty patients (n = 38 males, 67 ⫾ 6 years, n = 41 coronary artery bypass grafts, n = 9 valve procedures and/or combinations) fulfilled the inclusion criteria (age 418 years, planned cardiac surgery procedure with use of cardiopulmonary bypass) and nonexclusion criteria (stoma, hemorrhoidal nodes, rectal cancer disease) and were prepared for rectal probe placement after induction of anesthesia. The characteristics and concomitant diseases reflected the usual cardiac surgery patient profiles (Table 1). Laxative measures (enema) were performed on the day before surgery to reduce fecal contamination. The probe was covered with a protective sheath coated with a local analgesic (Xylocain 2%, AstraZeneca, Wedel, Germany) and placed at a depth of 5-10 cm in the rectal ampulla with the aid of an introducer rod under digital control. The correct position and signal transmission were checked by observing the biphasic curve pattern. After monitoring was initiated, general anesthesia was induced (0.3-1 mg/kg of sufentanil (Sufenta, Janssen-Cilag GmbH, Neuss, Germany), 1-2.5 mg/kg of propofol (Disoprivan, AstraZeneca GmbH, Wedel, Germany), and 0.6 mg/kg of rocuronium (Esmeron, Essex GmbH, Munich, Germany). For maintenance of general anesthesia, all patients received 1 to 2 vol% sevoflurane (Sevoran, Abbott, Wiesbaden, Germany) and intermittent boluses of sufentanil. Isotonic crystalloid (Sterofundin, B. Braun GmbH, Melsungen, Germany) was infused perioperatively based on institutional standards. The indication for red blood cell transfusion was a hemoglobin o7.5 mg/dL. The extracorporeal circuit included a membrane oxygenator (Quadrox oxygenator, Maquet Cardiopulmonary AG, Hirrlingen, Germany) and a roller pump system (HL20. Maquet Cardiopulmonary AG) equipped with a cardioplegia heat exchanger (Plegiox, Maquet Cardiopulmonary AG). The circuit was primed with 1,250 mL of crystalloid solution (Sterofundin, B. Braun Melsungen AG, Melsungen, Germany) according to institutional standards. Heparin (HeparinNatrium Braun, B.Braun Melsungen AG) was administered to maintain an activated coagulation time (ACT) greater than 400 seconds. During cardiopulmonary bypass (CPB), nonpulsatile flow was maintained at 2.6 to 3 L/min/m2, and mean arterial pressure (MAP) was maintained at 50 to 70 mmHg by the administration of norepinephrine (Arterenol, Sanofi-Aventis GmbH, Hoechst, Germany). Myocardial protection was achieved with cold blood cardioplegia (201C). Extracorporeal circulation was performed under mild hypothermia (321C). On completion of surgery, the patients were warmed and weaned from CPB.
Table 1. Patient (n ¼ 50) Demographic Characteristics, Intraoperative Data, and Postoperative Course Age, years Male NYHA class ZIII Elective surgery ASA class 42 LV function o30% Diabetes type II CPB (min)) CCT (min) Operation time (min) CABG In-hospital mortality 30-day mortality Redo-thoracotomy Mesenteric ischemia
67 ⫾ 6 38/50 19/50 50/50 11/50 2/50 31/50 120 ⫾ 48 min 73 ⫾ 41 min 244 ⫾ 54 min 41/50 2/50 2/40 4/50 0/50
Abbreviations: ASA, American Society of Anesthesiologists; CABG, coronary artery bypass graft; CCT, cross-clamp time; CPB, cardiopulmonary bypass; LV, left ventricle; NYHA, New York Heart Assocation.
To reverse the anticoagulant effects of heparin, protamine sulfate (Protaminsulfat, Novo Nordisk Pharma GmbH, Vienna, Austria) was administered, guided by the ACT.8 The optical method used for measuring relative blood flow by laser Doppler, hemoglobin amount, and hemoglobin oxygenation has been described in detail in the literature.11 In brief, the micro-light guide spectrophotometer O2C (Oxygen to See; LEA Medizintechnik, Giessen, Germany) transmits continuous laser light (830 nm and 30 mW) and white light (20 W, 500-800 nm, 1 nm resolution) to the tissue where it is scattered and collected at the surface (Fig 1). The collected light is split into its spectral components by a charge-coupled device array and is converted into an electrical signal. The laser Doppler shift is detected, and the product of moving erythrocytes and the time velocity of each erythrocyte are used to calculate the relative rectal blood flow (RBF). White light is used for the detection of oxygen saturation (SO2) and relative amount of hemoglobin (rHb). The tissue hemoglobin value is determined by the amount of light absorbed by the tissue. This measurement represents a hemoglobin concentration per tissue volume and is independent of vessel density, vessel lumen, and hemoglobin quantity in the blood.7 The change in color of the reflected light is due to wavelength-dependent absorption of the applied white light and can be used to calculate the oxygen saturation of hemoglobin. Adjustment of the distance between the application of the light and the detection of the reflected light allows detection in different tissues.8,9 In the present study, a newly developed transrectal probe (LFX 8, LEA Medizintechnik, Giessen, Germany) was placed before draping the patient in the operating room and was removed at the end of surgery. Rectal blood flow, rHb, and SO2 measurements were performed continuously (Fig 2). Interpretation of the measured results in the direct time interval was difficult. A high amplitude interval within the 1-second measurement cycles results in a large spread, which impedes an assessment of the measured values for SO2, rHb, flow, and velocity. Calculation of the arithmetic means of the measured values for 5-minute intervals greatly improves on-screen interpretation of the measured values (Fig 3). For statistical processing, the means of the time intervals t1 ¼ pre-pump, t2 ¼ cross-clamp, and t3 ¼ reperfusion were calculated for all 39 patients. The evaluation and graphical presentation of the recorded data were performed with tables and line charts using Excel 2010 (Microsoft Corporation, Redmond, WA) and the statistics program SPSS 21.0 (IBM, Chicago, IL), which also was used for the statistical analysis. The data sets were evaluated by calculating the mean and standard deviation of all data sets. Two sample dependent t tests for comparing means were used according to their function. An error probability of p o 0.05 was defined by consensus as statistically significant. No sample size calculation was performed for this one-arm diagnostic pilot study. Patients gave written informed consent (Clinical Trials Gov No.: NCT01425931 /Ethics Committee No.: 318/11). RESULTS
Because of patient disinfection, preparation for surgery, or fecal contamination, 11 patients experienced dislocation of the probe and loss of adequate signal strength. These were mainly coronary artery bypass graft procedures in which the legs were raised for disinfection before harvesting of venous bypass grafts. To avoid jeopardizing the sterility of the operative field, no repeat placement was attempted. None of the patients showed a proberelated complication. All of the patients had to be stabilized with vasopressors during perfusion to increase the MAP (norepinephrine, mean 0.08 μg/kg/min, range 0.05-0.5 μg/kg/min). No patient developed mesenteric ischemia or other gastrointestinal complications during the postoperative course. In-hospital mortality was 4%.
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Fig 1. The O2C device for the measurement of regional capillary venous rectal blood flow (rvRBF), oxygen saturation (srvO2), and hemoglobin concentration (rvHb); and the measurement principle of the O2C device is based on combined photospectrometry and laser Doppler flowmetry. Reprinted with the permission of LEA Medizintechnik GmbH, Giessen, Germany.
O2 saturation decreased on startup of CPB (68.14% ⫾ 19.9%) and also remained below baseline after opening the aortic clamp (65.07% ⫾ 16%). However, the values do not differ significantly (p ¼ 0.52). The fall both in SO2 and rHb possibly may be explained by hemodilution. The decrease is dependent on the duration of perfusion, but not on the start of CPB (Fig 4 and Table 2). The decrease in the relative Hb value also appeared to be hemodilution-related. The indication for transfusion during CPB was present at a critical Hb value of 7.5 mg/dL. The sensitivity of the O2C device was not sufficient to detect the administration of red blood cell concentrates with rectal measurement. Altogether, 5 of 39 patients received 1.2 units of red blood cells on average (range 1-3) during perfusion. The kinetics resemble
Fig 2. Novel rectal probe LFX8 designed to meet the special positioning requirements (special probe for stable measurements and anatomic design).
those of SO2 and flow: A decrease during perfusion and persistently low during the reperfusion phase without differing significantly from each other (Fig 4 and Table 2). The rectal microcirculation flow/velocity decreases with the duration of perfusion and reaches its lowest level before opening the aortic clamp. No significant differences were calculated (Fig 4 and Table 2). The microcirculation should be unimpaired by the hemodilution and can be interpreted as an effect of the perfusion. DISCUSSION
Laser Doppler Flowmetry (LDF) has been used to assess mucosal blood flow and a range of functions at different sites. Ohri et al studied the effect of CPB on the gastric mucosa of adults.9 They used a probe, positioned in the gut after retrograde insertion in a nasogastric tube. This enabled laser Doppler measurements to be taken with increased stability. Observations included profound reductions in mucosal blood flow during the hypothermic phase of CPB despite maintenance of MAP and flow. A close relationship between core temperature and gastric mucosal blood flow was found, and also between arterial pressure and gastric blood flow. Booker et al assessed the effect of CPB on neonatal gut mucosal blood flow at the rectum and investigated the effect of hypothermia/rewarming; it was found that neonates requiring aortic arch surgery may be at particular risk of gut mucosal hypoxia before and after surgery; with regard to temperature, laser doppler flowmetry (LDF) was reduced during cooling but was lowest during the rewarming phase.10,11 Emmanuel and Kamm12,13 found LDF to be highly reproducible and studied the effect on rectal mucosal blood flow of eating, smoking, body size, sex,
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Fig 3. Top: Raw data presentation with difficult visual interpretation of the time course with 1-second measurement points with high variability. Bottom: Plotting of means at 5-minute intervals improves visual interpretation of the measured results.
ovulatory status, and menstrual phase. Changes in mucosal blood flow induced by autonomically active drugs and nerve stimulation confirmed the role of the mucosal microcirculation as a measure of extrinsic nerve activity.12,13 Emmanuel et al,14 using LDF in a similar way, showed that patients with idiopathic constipation have impaired extrinsic gut nerve activity, particularly in those with slow transit. Hajivassiliou et al assessed blood flow distributions in the human colon during operations on 6 controls and 6 patients with inflammatory bowel disease undergoing colectomy; ischemia demarcation lines were identified before the onset of visible changes.15,16 But directly available monitoring of sufficient perfusion during extracorporeal circulation continues to be a major challenge.16 The monitoring of organ systems below skin level is especially a problem that, in many respects, has not been solved. In principle, laser Doppler, nailfold videomicroscopy, sidestream dark field imaging technique, SvO2, near-infrared spectroscopy, tonometry, sublingual capnometry, and microdialysis are available as possible bedside methods.17 However, none of these techniques allows intestinal diagnostic testing. A procedure already established outside rectal monitoring is lightguide tissue spectrophotometry with the instrument type
O2C. Clinical experience with O2C has been gathered in the following clinical fields: Arterial occlusive disease, wound healing disorders, inflammatory processes, compression control, amputation diagnostic testing, polyneuropathy, plastic surgery, and cardiac surgical applications for radial artery removal and mammary artery dissection.18,19 The design of a new probe made monitoring of the rectal microcirculation possible for the first time. The rationale of this pilot study was to evaluate the practicability and effectiveness of the new probe. Data were to be recorded continuously in 50 patients throughout the entire course of the operation. In 11 of 50 patients, fecal contamination or positional manipulations resulted in discontinuation of the measurement. The gravitational force of the probe head should be sufficient to retain the probe in position. Any type of assistive device that exerts additional pressure (eg, balloon catheter) on the probe head impairs the microcirculation and makes an assessment impossible. Firstly, therefore, sufficient preoperative bowel emptying should be ensured, and secondly, the patient’s passive movements during sterile washing should be executed only with great caution. The position of the probe remains to be discussed as a critical factor. The rectum has an anatomically different supply circulation compared with the rest of the large
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Fig 4. Mean and SD line of flow, rHb, velocity, and SO2 at the time points pre-pump, cross-clamp, and reperfusion. Increasing values after aortic cross-clamp without any recovery after removal and reperfusion.
intestine. For example, a large part of the rectum is supplied from the iliac artery and not from the inferior mesenteric artery, which is much more clinically relevant for intestinal ischemia. However, placing the probe intraluminally such that
the arterially-supplied area has changed is not possible under digital control. Endoscopic support would be necessary for this purpose but is ruled out as a routine measure because of its invasiveness.
Table 2. Overview of O2C Measured Values (SO2, rHb, flow, velocity) at 3 Different Time Points (Pre-pump, Cross-clamp, and Reperfusion) (n ¼ 39 Patients). Changes in Mean Among the 3 Time Points Were Not Significantly Different.
SO2 (%) Prepump Cross-clamp Reperfusion rHb (AU) Prepump Cross-clamp Reperfusion Flow (AU) Prepump Cross-clamp Reperfusion Velocity (AU) Prepump Cross-clamp Reperfusion
Mean
SD
Minimum
Maximum
Statistics
70.07 68.14 65.07
14.837 18.994 16.096
34 23 23
91 93 92
n.s.
42,10 39.38 35.79
10.510 12,031 10.594
22 15 18
64 62 68
n.s.
92,793 74.034 74.586
52,0227 37.6947 37.7014
20.0 6.0 16.0
280.0 195.0 190.0
n.s.
20.00 18.55 18.93
7.036 3.906 4.559
13 14 13
46 31 34
n.s.
Abbreviations: AU, arbitrary unit; n.s., not significant; rHb; sd, standard deviation.
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An alternative localization could be a buccal or sublingual measurement. Correlations between the sublingual microcirculation and mesenteric blood flow have been shown in intensive medical care studies in septic patients. The development of a buccal or sublingual probe possibly may offer advantages over rectal measurement. Advantages would include the possibility of correcting the position during an ongoing operation,
independence of the rectal evacuation status, and more substantial information about the intestinal blood flow. ACKNOWLEDGMENTS The authors thank Mrs. Sonja Friese (Study Coordinator, Goethe University Hospital, Frankfurt, Germany) for her assistance with the patient recruitment and data analysis.
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