Optimizing remote ischemic conditioning (RIC) of cutaneous microcirculation in humans: Number of cycles and duration of acute effects.

OBJECTIVE: Non-invasive Remote Ischemic Conditioning (RIC) offers an approach to reduce tissue damage in various organs/tissues. Besides attenuation of Ischemia-Reperfusion injury (I/R), beneficial effects on cutaneous microcirculation of free microsurgical flaps have been reported. Given the recency of this technique, there are considerable gaps in the current understanding of its mechanism of action. As a result, clinical transfer of RIC is prolongated in several fields. We aimed to optimize the RIC protocol by examination of different RIC-cycle numbers and its effect on changes of cutaneous microcirculation and duration. METHODS: 80 subjects were divided into groups (1, 3, 5, 7 RIC cycles). RIC was applied via an inflatable tourniquet. Cutaneous microcirculation was continuously assessed at the contralateral anterior lateral thigh utilizing a ©O2C-device continuously. RESULTS: RIC caused significant and sustained changes in microcirculation. Four hours after completion of RIC, a maximum increase of +80.8% (CI 1.395-2.221) in blood flow and +23.5% (CI 1.098-1.372) in tissue oxygen saturation was measured (three-cycle group). A higher number of applied cycles was accompanied with significant higher mean pain. CONCLUSION: Acute improvement of cutaneous microcirculation due to RIC lasted for at least 4 h after completion of the RIC-protocol. Dose-dependent effects of RIC are likely. With regard to the increase in pain, we recommend a RIC protocol of 3 cycles for future clinical application.

Anesthesia of the conditioned limb does not abolish the remote ischemic conditioning stimulus on cutaneous microcirculation in humans.

BACKGROUND: Mechanism of remote ischemic conditioning (RIC) remain not fully understood yet. Thus, a clinical trial was performed to assess the neuronal influence on its signal induction. METHODS: RIC was conducted on 45 patients who were randomized into 3 groups. Group A and B underwent brachial plexus anesthesia while RIC was performed on the blocked (A) and non-blocked side (B), respectively. In group C, RIC was conducted before regional anesthesia, thus serving as control group. All measurements were taken contralateral to RIC. The relative increase of microcirculatory parameters compared to baseline was evaluated and compared between the groups. RESULTS: Superficial blood flow (sBF) significantly increased in group A and C but values were higher among group C. Compared to group A, group C showed a significant increase of sBF during the initial 5 minutes of reperfusion (1.75; CI 1.139 - 2.361 vs. 0.97, CI 0.864 - 1.076, p < 0.05). Deep blood flow, tissue oxygen saturation and relative hemoglobin content were marginally influenced by RIC irrespectively of the presence of regional anesthesia. CONCLUSION: Despite regional anesthesia a significant RIC stimulus can be induced although its microcirculatory response is attenuated compared to control. Hence, RIC induction does not merely depend on neuronal signaling.

[Antibiotic treatment of infections in burn patients - a systematic review]. / Antibiotikatherapie von Infektionen bei Verbrennungspatienten ­ Eine systematische Übersichtsarbeit.

BACKGROUND: Due to the loss of the natural skin barrier function with reduced immune competence as a result of a plasma loss and the numerous intensive care interventions, burn patients are particularly at risk for infection. STUDY DESIGN: systematic review METHODS: A systematic review of German and English literature between 1990 and 2018 analyzes the epidemiological and diagnostic aspects as well as the therapeutic use of antibiotics in infections of burn patients in clinical trials. RESULTS: A total number of 53 randomized controlled clinical trials met the inclusion criteria. Various types / forms of application of antibiotic prophylaxis in burn wounds were investigated: topically, systemically (generally), systemically (perioperatively), nonabsorbable antibiotics (= selective intestinal decontamination), locally (inhaled) and all forms of administration versus control. Early postburn prophylaxis was studied in low-severity patients (six studies) and severe burn patients (seven studies). Antimicrobial prophylaxis has shown no effectiveness in the prevention of toxic shock syndrome in low grade burns, but can be useful in patients with severe burns in need for mechanical ventilation. Perioperative prophylaxis has been studied in ten studies. CONCLUSION: The benefit of long-term systemic antibiotic prophylaxis in the majority of burn patients is not evident. Mild infections in stable clinical conditions should be closely monitored, while in severe infections, international sepsis guidelines and the Tarragona principle are recommended.

[Soft tissue sarcomas: limb salvage using reconstructive plastic surgery techniques]. / Weichgewebssarkome: Extremitätenerhalt durch plastisch-rekonstruktive Verfahren.

The treatment of choice for soft tissue sarcomas with local involvement is still the complete surgical removal into healthy tissue. The aim of surgery is to achieve tumor-free resection margins in the sense of a R0 resection. No other treatment option can equally replace this important oncological condition. The enormous development in the field of reconstructive plastic surgery and in particular the advances in flap techniques and microsurgery enable limb salvage and the functional reconstruction even in the case of extensive tumors.

Improvement of local microcirculation through intermittent Negative Pressure Wound Therapy (NPWT).

BACKGROUND: Negative Pressure Wound Therapy (NPWT) is widely used across different kinds of surgical disciplines. A controversial debate was raised by diverging results from studies that were conducted to examine the impact of NPWT on local perfusion. Thus, there is a lack of evidence for one important underlying factors that influences the physiology of wound healing under an applied NPWT-dressing. OBJECTIVE: To investigate the immediate local perfusion changes due to an applied intermittent NPWT protocol. MATERIAL AND METHODS: A NPWT dressing was applied to the antero-lateral thigh of seven healthy volunteers with two probes of both pressure and microcirculatory measuring devices. One of each probe was placed under the NPWT dressing, the other one in close proximity next to it. A protocol consisting of two cycles of 10 min of -125 mmHg pressure, followed by 10 min of 0 mmHg pressure was applied. Measurements of local pressure to the underlying tissue, as well as microcirculatory changes were performed continuously. RESULTS: Applied vacuum caused compressional forces (27.33 mmHg, p < 0.05) towards the underlying tissue. Blood Flow was increased after both suction periods (+52.5%, +108.7%; p < 0.05) and continued increasing until the end of measurements (+145.3%). This was accompanied by significant increase in Oxygen Saturation (+21.6%; p < 0.05) and Relative Hemoglobin Content (+16.7%). Red Blood Cell Velocity was found to be increased without statistical significance. Next to the dressing, changes were also significant but less pronounced. CONCLUSION: Intermittent NPWT improves local microcirculation with consecutive enhancement of oxygen supply.

Sternal Reconstruction with the Omental Flap-Acute and Late Complications, Predictors of Mortality, and Quality of Life.

BACKGROUND: The omental flap is a reliable flap for the coverage of sternal defects. However, little is known about the predictors of mortality and the long-term outcome in such patients. METHODS: We, therefore, performed a retrospective study from 2002 to 2013, including all patients who underwent sternal reconstruction with the omental flap. RESULTS: A total of 50 patients were identified and mean follow-up was 3.8 years. Patient data was collected from the charts and 14 patients were available for telephone interviews. The majority of patients suffered from deep sternal wound infections. There was no complete flap loss and an overall success rate was 96%. In-hospital mortality was 14% and overall survival over follow-up was 50%. Significant predictors of mortality were age > 65, American Society of Anesthesiologists' status, defect size, prolonged ventilation, and the need for tracheotomy. Postoperative quality of life was reduced compared with other cohorts, especially with regard to bodily function. Pain was also a major problem for most patients along with herniation. CONCLUSION: The omental flap is a safe option even in patients with severe comorbidities. However, based on the data in this study, we would recommend the omental flap as a reserve option rather than first-line treatment for sternal defects.

[Remote Ischemic Conditioning - Endogenous Tissue Protection and its Possible Applications in Surgery]. / Remote ischemic Conditioning ­ endogene Gewebeprotektion und ihre Einsatzmöglichkeiten in der Chirurgie.

Tissue perfusion is pivotal to wound healing and tissue regeneration after surgery. Ischemia and reperfusion lead to inflammatory reactions with consecutive tissue damage and necrosis. Multiple conditioning techniques have been described to protect tissue from those damaging mechanisms in the perioperative period. However, most of these fail to meet the requirements of a good therapeutic effect, time and cost efficiency, non-invasiveness and applicability without the need for additional devices or drugs. Remote ischemic conditioning (RIC) is a technique to provide endogenous tissue protection, which fully meets those requirements. Repeated, short cycles of ischemia/reperfusion applied to a circumscribed vascular territory lead to the activation of endogenous signal pathways resulting in increased tolerance to hypoperfusion and limiting the damage caused by reperfusion, even in tissues located far away from the conditioned area. The non-invasive application of the conditioning stimulus requires no more than a pressure cuff, which is placed on the upper arm and is repeatedly inflated to suprasystolic pressures. Different concepts of remote ischemic pre-, peri- and postconditioning enable the usage in both elective and emergency surgical interventions. Based on encouraging experimental studies, the application of RIC has increased in the clinical setting. In addition to studies addressing cardio-, nephro- or neuroprotection there are some initial findings supporting a potential beneficial application in reconstructive microsurgery. This article aims to give an overview of the development, concepts and mechanisms of RIC with a focus on its clinical application in the field of surgery.

Ten minutes of ischemia is superior to shorter intervals for the remote ischemic conditioning of human microcirculation.

BACKGROUND: Surgical flaps have become reliable tools in the microsurgical armamentarium, but are still faced with tissue loss due to impaired perfusion which can lead to complete flap failure. Remote Ischemic Conditioning (RIC) has been demonstrated to be an effective way to improve microcirculation in surgical flaps in humans. However, little is known about the optimal amount and length of RIC cycles. OBJECTIVE: Determination of a superior protocol for RIC of cutaneous microcirculation in humans. METHODS: 60 healthy volunteers were randomized into different groups and received a RIC protocol, consisting of three cycles of either 1 second, 1, 5, or 10 minutes of ischemia followed by ten minutes of reperfusion. RIC was applied with a inflatable tourniquet placed on the upper arm. Changes in microcirculation were assessed via combined laser doppler/spectroscopy (O2C device) at the anterior lateral thigh. Relative increase at the end of conditioning vs. baseline measurements was calculated and compared between groups. RESULTS: RIC caused significant changes in cutaneous microcirculation (p < 0.05) which were more pronounced in groups with longer ischemia intervals. The ten minutes group was significantly superior. CONCLUSION: A conditioning protocol containing three cycles of ten minutes of ischemia is superior to protocols with shorter ischemia intervals for RIC of cutaneous microcirculation.

Upper extremity ischemia is superior to lower extremity ischemia for remote ischemic conditioning of antero-lateral thigh cutaneous blood flow.

Remote ischemic conditioning (RIC) is known to improve microcirculation in various settings, but little is known about the impact of the amount of ischemic tissue mass or the limb itself. Since ischemia and subsequent necrosis of flaps is one of the most dreaded complications in reconstructive surgery, adjuvant methods to improve microcirculation are desirable. We therefore performed a randomized trial to compare the effect of arm versus leg ischemia for RIC of the cutaneous microcirculation of the antero-lateral thigh. Forty healthy volunteers were randomized to undergo 5 min of ischemia of either the upper or lower extremity, followed by 10 min of reperfusion.Ischemia was induced by a surgical tourniquet applied to the proximal limb, which was inflated to 250 mmHg for the upper and 300 mgHg for the lower extremity. This cycle was repeated a total of three times. Cutaneous microcirculation was assessed by combined laser doppler spectrophotometry on the antero-lateral aspect of the thigh to measure cutaneous blood flow (BF), relative hemoglobin content (rHb), and oxygen saturation (StO2). Baseline measurements were performed for 10 min, after which the ischemia/reperfusion cycles were begun. Measurements were performed continuously and were afterwards pooled to obtain a mean value per minute. Both groups showed significant increases in all three measured parameters of cutaneous microcirculation after three cycles of ischemia/reperfusion when compared to baseline (BF: 95.1% (P < 0.001) and 27.9% (P = 0.002); rHb: 9.4% (P < 0.001) and 5.9% (P < 0.001), StO2: 8.4% (P = 0.045) and 9.4% (P < 0.001). When comparing both groups, BF was significantly higher in the arm group (P = 0.019 after 11 min., P = 0.009 after 45 min). In conclusions, both ischemic conditioning of the upper and lower extremity is able to improve cutaneous BF on the ALT donor site. However, RIC of the upper extremity seems to be a superior trigger for improvement of cutaneous BF.