Resuscitation Period Research Articles

Analysis of skeletal muscle microcirculation in a porcine polytrauma model with haemorrhagic shock.

Polytraumatised patients with haemorrhagic shock are prone to develop systemic complications, such as SIRS (systemic inflammatory response syndrome), ARDS (acute respiratory distress syndrome) and MOF (multiple organ failure). The pathomechanism of severe complications following trauma is multifactorial, and it is believed that microcirculatory dysfunction plays an important role. The aim of this study was to determine the changes in the microcirculation in musculature over time during shock and subsequent resuscitation in a porcine model of haemorrhagic shock and polytrauma. Twelve pigs (German Landrace) underwent femur fracture, liver laceration, blunt chest trauma, and haemorrhagic shock under standard anaesthesia and intensive care monitoring. Microcirculation data were measured from the vastus lateralis muscle using a combined white light spectrometry and laser spectroscopy system every 15 min during the shock and resuscitation period, and at 24, 48, and 72 h. Oxygen delivery and oxygen consumption were calculated and compared to baseline. The relative haemoglobin, local oxygen consumption, and saturation values in the microcirculation were observed significantly lower during shock, however, no changes in the microcirculatory blood flow and microcirculatory oxygen delivery were observed. After resuscitation, the microcirculatory blood flow and relative haemoglobin increased and remained elevated during the whole observation period (72 h). In this study, we observed changes in microcirculation during the trauma and shock phases. Furthermore, we also measured persistent dysfunction of the microcirculation over the observation period of 3 days after resuscitation and haemorrhagic shock. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1377-1382, 2018.

Goal-Directed Fluid Resuscitation Protocol Based on Arterial Waveform Analysis of Major Burn Patients in a Mass Burn Casualty

Adequate fluid titration during the initial resuscitation period of major burn patients is crucial. This study aimed to evaluate the feasibility and efficacy of a goal-directed fluid resuscitation protocol that used hourly urine output plus the arterial waveform analysis FloTrac (Edwards LifeSciences, Irvine, Calif) system for major burns to avoid fluid overload. We conducted a retrospective cohort study of 43 major burn patients at the Tri-Service General Hospital after the Formosa Fun Coast Dust Explosion on June 27, 2015. Because of the limited capacity of intensive care units (ICUs), 23 intubated patients were transferred from the burn wards or emergency department to the ICU within 24 hours. Fluid administration was adjusted to achieve a urine output of 30 to 50 mL/h, cardiac index greater than 2.5 L/min/m, and stroke volume variation (SVV) less than 12%. The hourly crystalloid fluid infusion rate was titrated based on SVV and hourly urine output. Of the 23 critically burned patients admitted to the ICU, 13 patients who followed the goal-directed fluid resuscitation protocol within 12 hours postburn were included in the analysis. The mean age (years) was 21.8, and the mean total body surface area (TBSA) burned (%) was 68.0. The mean Revised Baux score was 106.8. All patients sustained inhalation injury. The fluid volumes administered to patients in the first 24 hours and the second 24 hours (mL/kg/% total body surface area) were 3.62 ± 1.23 and 2.89 ± 0.79, respectively. The urine outputs in the first 24 hours and the second 24 hours (mL/kg/h) were 1.13 ± 0.66 and 1.53 ± 0.87, respectively. All patients achieved the established goals within 32 hours postburn. In-hospital mortality rate was 0%. The SVV-based goal-directed fluid resuscitation protocol leads to less unnecessary fluid administration during the early resuscitation phase. Clinicians can efficaciously manage the dynamic body fluid changes in major burn patients under the guidance of the protocol.

Effect of Severe Traumatic Hemorrhage on Large Arterial Diameter as Determined by Computed Tomography

Background: The objective of this study was to investigate changes in the diameters of major arteries in trauma patients at the time of severe intravascular volume depletion.Methods: Patients admitted from January 2008–June 2017 in extremis or in arrest who had an immediate computed tomography (CT) scan in the resuscitation period and at least one subsequent CT scan after hemodynamic stabilization and admission to the intensive care unit were included. Diameter in millimeters (mm) of the common carotid, subclavian, common iliac, external iliac, common femoral arteries, and aorta at the following locations were obtained: ascending, proximal descending, and mid-descending thoracic and supra-celiac, renal, and aortic bifurcation.Results: Fourteen patients (93% male) were included. Mean injury severity score was 37 ± 8 and age 36 ± 18 years. Ten patients received a resuscitative endovascular balloon occlusion of the aorta and four patients received a resuscitative thoracotomy prior to the first CT. A maximum increase of the aorta of 63.6%, and 116.9% in the common carotid, subclavian, common iliac, external iliac, and common femoral arteries was observed. For patients aged 18–39 years, increases in diameter were statistically significant (p < 0.05) at all locations except the peri-renal aorta and left subclavian. Patients ≥40 years had a less robust change, with a significant diameter increase only with the proximal descending aorta (p = 0.02).Conclusions: Large arterial diameters in the setting of severe hemorrhage are significantly reduced particularly in younger patients. This has significant implications for emergent placement of endovascular devices such as introducer sheaths, balloon catheters, and stent grafts where the determination of arterial diameter is critical.

Full neurological recovery following a hypothermic, near-drowning cardiac arrest with a 34 minute submersion time: A case repor

Hypothermia increases the ischemic tolerance of the brain and can lead to a remarkable recovery in prolonged cardiac arrest. Neurological outcomes can be very favorable, particularly if cardiac arrest precedes hypothermia or if the onset of hypothermia following cardiac arrest is rapid. Case reports of good neurological recovery following up to 7 h submersion and core temperatures as low as 13.7°C can be found. Our case involved a 43-year-old male who presented following a collapse and out of hospital cardiac arrest. A 34 min period of face-down submersion in a canal on a cold February evening was followed by a brief period of cardiopulmonary resuscitation on extrication. He was transferred to our emergency department with a core temperature of 26°C. He went onto make a full neurological recovery. The UK’s temperate climate means that case reports of prolonged hypothermic cardiac arrest are rare. While this gentleman had many favorable circumstances to his predicament, including age, cardiovascular fitness and rapid cooling, prompt and effective resuscitation, and a controlled warming regime would also have contributed. Keywords: Hypothermia cardiac arrest, neurological recovery.

Spectral analysis of heart rate variability predicts mortality and instability from vascular injury

BackgroundSpectral analysis of continuous blood pressure and heart rate variability provides a quantitative assessment of autonomic response to hemorrhage. This may reveal markers of mortality as well as endpoints of resuscitation. MethodsFourteen male Yorkshire pigs, ranging in weight from 33 to 36 kg, were included in the analysis. All pigs underwent laparotomy and then sustained a standardized retrohepatic inferior vena cava injury. Animals were then allowed to progress to class 3 hemorrhagic shock and where then treated with abdominal sponge packing followed by 6 h of crystalloid resuscitation. If the pigs survived the 6 h resuscitation, they were in the survival (S) group, otherwise they were placed in the nonsurvival (NS) group. Fast Fourier transformation calculations were used to convert the components of blood pressure and heart rate variability into corresponding frequency classifications. Autonomic tones are represented as the following: high frequency (HF) = parasympathetic tone, low frequency (LF) = sympathetic, and very low frequency (VLF) = renin-angiotensin aldosterone system. The relative sympathetic to parasympathetic tone was expressed as LF/HF ratio. ResultsBaseline hemodynamic parameters were equal for the S (n = 11) and NS groups. LF/HF was lower at baseline for the NS group but was higher after hemorrhage and the resuscitation period indicative of a predominately parasympathetic response during hemorrhagic shock before mortality. HF signal was lower in the NS group during the resuscitation indicating a relatively lower sympathetic tone during hemorrhagic shock, which may have contributed to mortality. Finally, the NS group had a lower VLF signal at baseline (e.g., [S] 16.3 ± 2.5 versus [NS] 4.6 ± 2.9 P < 0.05,) which was predictive of mortality and hemodynamic instability in response to a similar hemorrhagic injury. ConclusionsAn increased LF/HF ratio, indicative of parasympathetic predominance following injury and during resuscitation of hemorrhagic shock was a marker of impending death. Spectral analysis of heart rate variability can also identify autonomic lability following hemorrhagic injuries with implications for first responder triage. Furthermore, a decreased VLF signal at baseline indicates an additional marker of hemodynamic instability and marker of mortality following a hemorrhagic injury. These data indicate that continuous quantitative assessment of autonomic response can be a predictor of mortality and potentially guide resuscitation of patients in hemorrhagic shock.

Vascular Damage Control Approach Using Direct Deployment of Self-Expandable PTFE Covered Stent as an Alternative to Intra-Arterial Shunt

The use of intravascular shunts for damage control purposes has been well described both in the battlefield and in the civilian environment. In this report, we present a case in which a self-expanding polytetrafl uoroethylene (PTFE) stent graft was used as an alternative to traditional damage control intra-arterial shunt to successfully control bleeding and reestablish arterial flow in the aortoiliac segment. A 50-year-old male presented in extremis after sustaining multiple abdominal gunshot wounds. After resuscitative thoracotomy, laparotomy demonstrated transection of the right common iliac artery at its origin, destructive pancreatoduodenal injury with associated superior mesenteric vein injury, and multiple small bowel and colonic injuries. Because of the location of the injury at the aortoiliac junction, temporary intra-arterial shunt placement was not possible as no residual iliac cuff was available to secure a tie around the shunt proximally. A self-expanding PTFE stent graft was introduced and directed across the injury under direct visualization and deployed to bridge the defect from the aortic bifurcation to the right common iliac artery. After deployment, the stent was hemostatic and pulses were palpable in bilateral iliac and common femoral arteries. The associated intra-abdominal injuries were addressed and the abdomen packed and temporarily closed. Total operative time was 65 minutes. After a 4-hour period of resuscitation in the ICU, the patient became hemodynamically unstable and was re-explored. Diffuse bleeding was identified in all raw surfaces of the retroperitoneum, abdominal wall and chest wall. The area of the stent was hemostatic. The right colon was massively dilated from intraluminal bleeding, so a right hemicolectomy was performed. Despite resuscitative eff orts and more than 100 units of blood products the patient expired. In this report, we described the use of direct endovascular repair using a self-expanding PTFE stent graft in the aortoiliac location as an alternative to temporary intra-arterial shunt placement. This technique allowed quick hemostasis and reestablishment of arterial flow in an area in which traditional intra-arterial shunts would not be feasible.

The time period of on-scene resuscitation in out of-hospital cardiac arrest patients transported without return of spontaneous circulation

The time period of on-scene resuscitation in out of-hospital cardiac arrest patients transported without return of spontaneous circulation

Acute Alcohol Binge Deteriorates Metabolic and Respiratory Compensation Capability After Blunt Chest Trauma Followed by Hemorrhagic Shock-A New Research Model.

The clinical relevance of blunt (thoracic) chest trauma (TxT) and hemorrhagic shock is indisputable due to the high prevalence of this injury type, as well as its close association with mortality and/or preventable deaths. Furthermore, there is an ongoing discussion about the influence of alcohol in trauma patients. Thus, we established a model of TxT followed by hemorrhagic shock with resuscitation (H/R) in alcohol-intoxicated rats. Depending on group allocation, 12 (subacute) or 2 (acute) hours before experimentation, the animals received a single oral dose of alcohol (ethanol [EtOH]) or saline (NaCl) followed by TxT, hemorrhagic shock (35±3mm Hg), and resuscitation (TxT+H/R). Arterial blood gas analyses and continuous monitoring of blood pressure were performed during the experimentation period. Survival during the experimentation procedure was determined. Subacute and acute EtOH group exhibited lower baseline mean arterial blood pressure values compared with the corresponding NaCl group, respectively. Both EtOH groups showed lower maximal bleed-out volume, which was necessary to induce hemorrhagic shock compared to NaCl groups, and the recovery during the resuscitation period was attenuated. During the experimentation in all groups, a trend to acidic pH was observed. Acute EtOH group showed lowest pH values compared to all other groups. Higher pCO2 values were observed in both EtOH groups. All groups developed negative base excess and decreasing HCO3- values until the end of hemorrhagic shock and showed increasing base excess and HCO3- values during resuscitation. Significantly higher mortality rate was found in the acute EtOH group. This study indicates that alcohol limits the metabolic and respiratory compensation capability, thereby promoting mortality.

Fluid Resuscitation in Septic Patients Improves Systolic but not Diastolic Middle Cerebral Artery Flow Velocity

To investigate the effects of fluid resuscitation on cerebral hemodynamics in sepsis, the following set of transcranial Doppler (TCD) parameters was used: maximal change in flow velocity (FV) during stroke onset (acc), maximal FV during first (sys1) or second (sys2) phase of systole and mean diastolic FV (dias@560). We aim to evaluate changes in cerebral hemodynamics that result from (i) sepsis and (ii) adequate fluid resuscitation in critically ill septic patients. In the majority of 16 septic patients sys2 was initially absent but reappeared during the period of fluid resuscitation; whereas sys2 absence was never seen in healthy controls. Second, adequate fluid resuscitation resulted in a significant increase of the systolic FV components (acc, sys1, sys2 and systolic blood pressure); whereas the diastolic components (dias@560 and diastolic blood pressure) remained unchanged. Sys2 absence and reappearance in sepsis suggests that TCD could become a non-invasive alternative for hemodynamic monitoring.

The modified ‘Jo'burg’ technique for securing intercostal chest drains

Insertion of an intercostal chest drain (ICD) is a common intervention in the management of either blunt or penetrating thoracic trauma. It is frequently performed by junior medical personnel as...

Free Trehalose Accumulation in Dormant Mycobacterium smegmatis Cells and Its Breakdown in Early Resuscitation Phase.

Under gradual acidification of growth medium resulting in the formation of dormant Mycobacterium smegmatis, a significant accumulation of free trehalose in dormant cells was observed. According to 1H- and 13C-NMR spectroscopy up to 64% of total organic substances in the dormant cell extract was represented by trehalose whilst the trehalose content in an extract of active cells taken from early stationary phase was not more than 15%. Trehalose biosynthesis during transition to the dormant state is provided by activation of genes involved in the OtsA-OtsB and TreY-TreZ pathways (according to RT-PCR). Varying the concentration of free trehalose in dormant cells by expression of MSMEG_4535 coding for trehalase we found that cell viability depends on trehalose level: cells with a high amount of trehalose survive much better than cells with a low amount. Upon resuscitation of dormant M. smegmatis, a decrease of free trehalose and an increase in glucose concentration occurred in the early period of resuscitation (after 2 h). Evidently, breakdown of trehalose by trehalase takes place at this time as a transient increase in trehalase activity was observed between 1 and 3 h of resuscitation. Activation of trehalase was not due to de novo biosynthesis but because of self-activation of the enzyme from the inactive state in dormant cells. Because, even a low concentration of ATP (2 mM) prevents self-activation of trehalase in vitro and after activation the enzyme is still sensitive to ATP we suggest that the transient character of trehalase activation in cells is due to variation in intracellular ATP concentration found in the early resuscitation period. The negative influence of the trehalase inhibitor validamycin A on the resuscitation of dormant cells proves the importance of trehalase for resuscitation. These experiments demonstrate the significance of free trehalose accumulation for the maintenance of dormant mycobacterial viability and the involvement of trehalose breakdown in early events leading to cell reactivation similar to yeast and fungal spores.

Trauma resuscitation: can team behaviours in the prearrival period predict resuscitation performance?

BackgroundOptimising team performance is critical in paediatric trauma resuscitation. Previous studies in aviation and surgery link performance to behaviours in the prearrival period.ObjectiveTo determine if patterns of human behaviour in...

Permissive Hypotension and Trauma: Can Fluid Restriction Reduce the Incidence of ARDS?

Emergency care, including the resuscitation of patients involved in traumatic events, has evolved over the years. A prior practice of utilizing large volumes of crystalloids has been found to contribute to complications such as coagulopathy, fluid overload, and adult respiratory distress syndrome (ARDS). In contrast, permissive hypotension is a method of fluid restriction that allows for low blood pressure and mean arterial pressure during the resuscitation period. When permissive hypotension occurs and fluids are restricted in trauma patients, the incidence of ARDS can be reduced significantly with improvement in patient outcomes. Using evidence, nurse practitioners in the emergency department have an important role in evaluating and updating protocols such as permissive hypotension.

Reperfusion Shutdown: Delayed Onset of Fibrinolysis Resistance after Resuscitation from Hemorrhagic Shock Is Associated with Increased Circulating Levels of Plasminogen Activator Inhibitor-1 and Postinjury Complications

▪Introduction: In the CRASH II trial, administration of tranexamic acid (TXA) >3 hours after injury was associated with increased mortality. Recent evidence indicates that fibrinolysis inhibition upon presentation to the emergency department (ED) is associated with increased mortality from organ failure. However, it remains unclear if fibrinolysis status changes in response to resuscitation. We hypothesize that the incidence of fibrinolysis resistance (shutdown) increases after resuscitation and is associated with increased post injury complications, prolonged respiratory failure, and prolonged ICU stay.Methods: Blood samples were collected prospectively on injured patients with documented prehospital shock (SBP < 90mm HG ) identified by the emergency medical service as part of an ongoing study to measure the impact of resusciation on coagulation in trauma. Patients had thrombelastography (TEG) samples drawn at admission and sequentially over 24 hours. Susceptibility to fibrinolysis was quantified using a tissue plasminogen activator (tPA) modified TEG. Fibrinolysis shutdown was defined as the lysis at 30 minutes (LY30) < 5thpercentile of healthy volunteers (n=160). Kaplan-Meier plot was generated to identify the timing and cumulative incidence of fibrinolysis shutdown in the first 24 hours after injury. Outcomes were contrasted between patients with and without shutdown at different time intervals from injury using a Mann Whitney U test to assess for 30 day post-injury complications, mechanical ventilator free days, and intensive care unit free days. A nested population of twelve patients that had elevated fibrinolysis activity on presentation to the emergency department and did not receive TXA were analyzed for endogenous tPA and plasminogen activator inhibitor-1(PAI-1) activity during their first 24 hours post injury, which also including pre hospital samples before resuscitation.Results: Ninety patients (median ISS of 27 and prehospital SBP of 72 mmHG) were included in the analysis, with a mortality rate of 13%. Overall, 76 % of patients developed fibrinolysis shutdown. Fifty percent of the population developed fibrinolysis shutdown within 2 hours of injury, and 75% of patients reached shutdown by 4 hours post injury (figure 1). Patients who remained in shutdown at 12 hours postinjury had significantly fewer ventilator free days (median 23 vs 26 p=0.005) and fewer ICU free days (median 20 vs 26 p= 0.004) with longer hospitalization (median 16 days vs 5 p=0.001). Patients in shutdown at 12 hours also had an increased incidence of in hospital complications (40% vs 15% p=0.048). Patients that were in fibrinolysis shutdown at 12 hours had increased plasma (p=0.010) platelet (p=0.007) and TXA (p=0.033) transfusions in the first 6 hours of resuscitation compared to those patients not in shutdown. In the nested cohort of patients with elevated LY30 upon presentation to the hospital, the median tPA activity peaked in prehospital samples (median 0.87 IU/ml) and decreased 10 fold by 4 hours postinjury (0.08 p<0.001), whereas PAI-1 activity increased 700 fold during the same time frame (0.04 to 175 IU/ml p<0.001).Conclusion: Fibrinolysis resistance becomes prevalent in injured patients with prehospital hypotension after successful resuscitation, and this is associated with markedly elevated levels of PAI-1. Patients with fibrinolysis shutdown 12 hours after injury have increased ventilator requirements and prolonged ICU stays. Extending the time patients are in fibrinolysis shutdown during the post resuscitation period appears to be a risk factor for protracted respiratory failure, and may explain why delayed administration of TXA is associated with increased mortality. These results suggest future therapeutic opportunities to reduce PAI-1 activity in the postinjury period to attenuate postinjury organ failure. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

N-Acetylcysteine and Desferoxamine Reduce Pulmonary Oxidative Stress Caused by Hemorrhagic Shock in a Porcine Model

ABSTRACTAim of the study: To investigate the pulmonary oxidative stress and possible protective effect of N-Acetylcysteine (NAC) and Desferoxamine (DFX)in a porcine model subjected to hemorrhagic shock. Materials and Methods: Twenty-one pigs were randomly allocated to Group-A (sham, n = 5), Group-B (fluid resuscitation, n = 8) and Group-C (fluid, NAC and DFX resuscitation, n = 8). Groups B and C were subjected to a 40-min shock period induced by liver trauma, followed by a 60-min resuscitation period. During shock, the mean arterial pressure (MAP) was maintained at 30–40 mmHg. Resuscitation consisted of crystalloids (35 mL/kg) and colloids (18 mL/kg) targeting to MAP normalization (baseline values ± 10%). In addition, Group-C received pretreatment with NAC 200 mg/kg plus DFX 2 g as intravenous infusions. Thiobarbituric Acid Reactive Substances (TBARS), protein carbonyls and glutathione peroxidase (GPx) activity were determined in lung tissue homogenates. Also, histological examination of pulmonary tissue specimens was performed. Results: TBARS were higher in Group-B than in Group-A or Group-C: 2.90 ± 0.47, 0.57 ± 0.10, 1.78 ± 0.47 pmol/μg protein, respectively (p < 0.05). Protein carbonyls content was higher in Group-B than in Group-A or Group-C: 3.22 ± 0.68, 0.89 ± 0.30, 1.95 ± 0.54 nmol/mg protein, respectively (p > 0.05). GPx activity did not differ significantly between the three groups (p > 0.05). Lung histology was improved in Group-C versus Group-B, with less alveolar collapse, interstitial edema and inflammation. Conclusion: NAC plus DFX prevented the increase of pulmonary oxidative stress markers and protein damage after resuscitated hemorrhagic shock and had beneficial effect on lung histology. NAC/DFX combination may be used in the multimodal treatment of hemorrhagic shock, since it may significantly prevent free radical injury in the lung.

プロテインS欠乏症を背景とする上腸間膜静脈血栓症によって心肺停止に至った1救命例(A case of cardiopulmonary arrest caused by superior mesenteric venous thrombosis associated with protein S deficiency)

症例は76歳の男性で，腹痛を主訴に前医を受診したところ，診察中に心肺停止状態となり，約10分間で蘇生し，当院へ転院となった。前医での腹部単純CTで腹水の貯留と小腸の浮腫像を認め，小腸壊死を疑い，緊急で試験開腹術を行った。Treitz靱帯より肛門側10cmから80cmまでの空腸が壊死しており，また腸間膜の静脈内には血栓が認められた。病変部の切除のみを行い手術を終了した。術後の腹部造影CTで上腸間膜内から門脈に伸展する血栓を認め，上腸間膜静脈血栓症と診断した。第3病日に再開腹すると，残存空腸の色調は良好であり，切除断端を吻合した。術後の経過は良好で，第42病日に退院した。血栓症の原因検索をしたところ，プロテインS抗原量46%，プロテインS活性36%と低下しており，欠乏症と考えられた。今回我々は，心肺停止に至ったが，手術を行い良好な経過を得たプロテインS欠乏症によるSMVTの1例を経験した。腸管虚血により心肺停止に至った症例で，早期に自己心拍再開が得られた場合は，積極的に手術を行い，原因疾患を治療することが重要である。 A 76–year–old man consulted a previous hospital with the chief complaint of abdominal pain. He lost consciousness followed by cardiopulmonary arrest, but recovered after 10 minutes of resuscitative efforts. He was then referred to our hospital. CT scan showed marked edema of the small intestinal wall and ascites. Emergency laparotomy was performed under the diagnosis of intestinal necrosis. Operative findings revealed congestive necrosis of the jejunum caused by thrombosis of the mesenteric vein. About 70 cm of the necrotic intestine was resected without anastomosis. Abdominal contrast–enhanced CT showed a thrombus in the superior mesenteric and portal vein. Based on the above findings, the patient was diagnosed as having superior mesenteric venous thrombosis (SMVT). Two days after the first operation, a second look operation showed no new necrotic lesions. The postoperative course was uneventful. Coagulation study showed a low protein S antigen (46%) and activity (36%). We report this case due to the rarity of cardiopulmonary arrest caused by SMVT associated with protein S deficiency. In the case of arrest caused by intestinal ischemia, particularly when return of spontaneous circulation after a short period of cardiopulmonary resuscitation is achieved, we should eliminate the cause of the cardiac arrest by surgery. 上腸間膜静脈血栓症（superior mesenteric venous thrombosis: SMVT）は急性腹症開腹例の0.1%以下 1と比較的稀だが，腸管のうっ血性循環障害から腸管壊死を引き起こし，死亡率は20–50%と高く致命的となり得る疾患である 2。今回我々は，心肺停止（cardiopulmonary arrest: CPA）に至ったが，緊急手術を行い良好な経過を得たプロテインS欠乏症によるSMVTの1例を経験したので報告する。 患 者：76歳，男性 主 訴：腹痛 既往歴：高血圧，下肢深部静脈血栓症（来院1年前，他院で指摘されワルファリンを開始した。来院3か月前，同院で血栓の消失を確認し，ワルファリンは終了した。） 常用薬：リマプロスト15μg/日，アムロジピン7.5mg/日，オルメサルタン20mg/日 家族歴：特記事項なし 現病歴：来院当日，腹痛の増悪と鮮血便を認めた。前医を受診し，処置中にCPAとなり，約10分間の蘇生処置により心拍が再開した。著明な代謝性アシドーシスと，腹部単純CTで腹水貯留と上部小腸の拡張を認め，小腸壊死が疑われ，当院へ紹介された。 現 症：JCS300，呼吸数31/分，脈拍107/分・整，血圧132/58mmHg，体温33.3°C，SpO2 89%（バッグバルブマスク換気，酸素10L/分）。瞳孔2.0mm/2.0mm，対光反射は両側とも迅速であった。腹部は膨隆し，板状硬であった。 血液検査：WBC 15,100/µL，Hb 20.3g/dL，Hct 61.3%，Plt 25.3×104/µL，AST 26U/L，ALT 28U/L，LDH 316U/L，CK 92U/L，BUN 26.3mg/dL，Cr 2.10mg/dL，Na 147mEq/L，K 4.9mEq/L，CRP 7.32mg/dL，APTT 79.1sec，PT活性47%，Fib 173mg/dL，D–dimer 88.5µg/mL，可溶性フィブリンモノマー複合体229.3μg/mL，AT III 24%，プロテインC活性15%，プロテインS活性12%，抗カルジオリピンβ2–GP1抗体 <1.2U/mL 動脈血液ガス分析（バッグバルブマスク換気，酸素10L/分）：pH 7.301，pO2 56.4mmHg，pCO2 41.3mmHg，HCO3− 19.8mmol/L，BE −5.8mmol/L，Lac 25mmol/L 腹部単純CT検査所見：肝周囲に腹水の貯留を認めた。上部小腸の拡張を認め，拡張腸管と連続する腸間膜静脈内に高吸収域を認めた（Fig. 1）。 Abdominal plain CT from previous hospital. a: Large amount of ascites. b: Wall of the small intestine was edematous. c, d: Mesenteric vein showed high density. 経 過：腹部単純CT検査所見より，小腸壊死が疑われ，救急外来で緊急開腹手術を施行した。開腹すると血性腹水を認め，空腸はトライツ靱帯より10cmから80cmの部分が暗赤色に変化し，腸間膜の肥厚を認めた。壊死腸管を切除し，吻合は行わず盲端のまま閉腹した。手術時間は69分で，術中輸血は赤血球濃厚液4単位と新鮮凍結血漿4単位を投与した。腸間膜を処理した際，腸間膜静脈内に血栓を認めた（Fig. 2）。摘出標本では，腸管および腸間膜は暗赤色に変化し浮腫性であり，腸管粘膜も暗赤色を呈していた。腸間膜静脈内に多数の血栓を認めたが，動脈に変化を認めなかった（Fig. 3）。手術後に撮影した腹部造影CT検査では，上腸間膜静脈の拡張とその内部に陰影欠損を認めた。欠損像は門脈まで伸展を認めた（Fig. 4）。上腸間膜静脈血栓症による小腸壊死とそれに伴う心停止と診断し，術後よりウロキナーゼ60,000単位/日，未分画ヘパリン10,000単位/日の持続投与による抗凝固療法を開始した。術後の血液検査でフィブリノーゲンが正常範囲内であったため，新鮮凍結血漿の投与は追加しなかった。また，心肺停止蘇生後脳症に対して，深部体温35.0°Cにて低体温療法を入院後48時間施行した。術後ICU入室時のAPACHE IIスコアは40点であった。第3病日，second look operationを施行し，腸管切除断端の血流が良好であることを確認し，端々吻合した。術後は重要臓器障害など認めず良好に経過し，第5病日に播種性血管内凝固症候群を離脱した。第7病日，意識レベルはGCS E4VTM6に回復した。第22病日，凝固線溶系検査を再度施行すると，プロテインS活性36%，抗原量46%で有意な低下を認め，AT III，プロテインC活性はいずれも正常値であった（Table 1）。本症例の家族も検査した結果，長女と次女も同様にプロテインS活性および抗原量の低下を認めたため，プロテインS欠乏症と診断した。第23病日，腹部造影CT検査にて上腸間膜静脈および門脈の血栓は縮小を認め，ワルファリン内服を開始した。第41病日，血栓の消失を認め，第42病日，前医へ転院となった。転院後もワルファリン内服による抗凝固療法を継続し，血栓症の再発なく経過している。 Operative findings. a: Congestive necrosis of the jejunum. b: Thrombus was found in the mesenteric vein. Macroscopic findings of resected specimen. a: Resected jejunum showed transmural necrosis. b: Massive thrombi were found in the mesenteric vein and but not found in the mesenteric artery. Abdominal enhanced CT after initial surgery. a, b: Thrombus in the superior mesenteric vein. c: Thrombus continued to the portal vein. SMVTは，静脈のうっ滞から腸管虚血を来す比較的稀な疾患であり，その発生頻度は腸間膜血管閉塞性疾患の5–15%を占め 2，急性腹症開腹例の0.1%以下と報告される 1。好発年齢は6歳から68歳（平均40歳）で男女比は32:15で男性に多いとされる 3。死亡率は20–50%と高く，年齢，発症から診断および手術施行までの時間が予後規定因子となる 2, 4。 SMVTの約80%は続発性であり，原因となり得る病態として，凝固線溶系の異常，血液疾患，腹部炎症疾患，開腹術，門脈圧亢進症，腹部外傷などが挙げられる 2。近年ではAT III，プロテインC，プロテインSなどの先天的欠損や低下が重要視されており，仲田らの報告 5では，本邦の上腸間膜静脈血栓症のうち29.3%で凝固線溶系異常を認めており，SMVTの患者に対して凝固線溶系異常を検索することは重要である。 SMVTの症状は，急性の経過では腸管の循環不全から腹痛を来す一方で，慢性の経過では側副血行路が発達し無症状なことが多いとされる。元々凝固障害を有している患者は血栓の伸展が緩徐であり側副血行路の発達がしやすいことから，凝固能が健常である患者と比較して死亡率が低くなる報告 6, 7もみられる。血液凝固異常による血栓は，腸管内の微小静脈から始まり粘膜に限局性壊死や出血性梗塞が起こる。徐々に中枢の静脈へ伸展し，本管が閉塞すると腸管壊死に陥り症状が激化すると推測される 2, 8。 SMVTの治療法は，亜急性や慢性の経過では血管の完全閉塞に至らず限局性壊死でとどまることがあるため，腸管壊死を疑う所見がない場合には抗凝固療法や血栓溶解療法による保存的治療を第一選択にすべきとする報告 2, 9がみられる。しかし，腸管壊死を伴う場合は開腹手術が不可欠である。壊死腸管切除の際，辺縁の肉眼的に正常な腸管にも血栓が広がっていることがあり，辺縁の正常腸管の切除範囲が問題となるが，切除範囲の明確な基準はない。SMVTの術後合併症は患者の55%に起こると言われ，最もよくみられる合併症の一つに短腸症候群がある。また血栓症の再発率は29%と高く，再発による死亡率は37%との報告 10もある。これらの合併症を防ぐために過不足のない腸管切除が求められるため，second look operationを行い，腸管のviabilityを確認し，腸管切除を最小限にとどめることが推奨されている 11。自験例は心停止蘇生後であり，侵襲を低くするため壊死腸管の切除は最低限にとどめ，48時間後にsecond look operationで新たな腸管壊死出現の有無を確認する方針とした。second look operationでは腸管壊死を認めることなく，端々吻合を行い，術後も血栓の再発やイレウスなどを認めることなく良好に経過した。 腸管虚血からのCPAは，虚血により腸管粘膜バリア機構が破綻して引き起こされるbacterial translocationや穿孔によるseptic shock，および水分電解質異常によるhypovolemic shockが関連すると考えられている。CPA蘇生後の症例に対する開腹手術に関して，森脇ら 12は，推定虚脱時間が4分以内，初回心電図リズムが心静止以外で，病院到着後10分以内の自己心拍再開があれば積極的に適応すべきだとしている。自験例では，来院時の血液検査でヘモグロビン20.3g/dLと著明な血液濃縮を認めていたことから，hypovolemic shockから代謝性アシドーシスとなりCPAに至ったと考えられた。しかし，院内CPA症例であり，迅速な蘇生処置の開始が行われ，推定虚脱時間は最小限ですみ，10分以内の自己心拍再開が得られた。自験例のように，速やかに蘇生が得られれば，原疾患の根本治療が循環動態および代謝環境の改善につながるため，積極的に手術治療を行う必要があると考えられた。 プロテインS欠乏症は常染色体優性遺伝形式をとり，発生頻度は欧米の0.2%に対し，日本では健常人の1–2%，静脈血栓症患者の18–22%を占め高い傾向にある 13。プロテインSは活性型プロテインCが，第VIIIa因子および第Va因子を失活化する際の補助因子として機能し，プロテインS活性低下により凝固制御がされず，易血栓性状態となる。プロテインS欠乏症患者の55%に血栓症が認められると報告 14されており，血栓症を全く起こさない例もある。血栓症の発症には後天的血栓性素因（手術，感染症，外傷，妊娠，長期臥床，薬剤，自己免疫性疾患）も複合的に関与すると考えられており，血栓症を発症していないプロテインS欠乏症患者に対して，予防的な抗凝固療法を施行すべきかは定まっていない 13。しかし，血栓症を発症したプロテインS欠乏症患者の再発率は高く，とくにSMVT手術例の術後再発率は77%と報告され，再発予防のために術後の抗凝固療法が必須である 15。自験例では，深部静脈血栓症の治療が終了した3か月後にSMVTを発症しており，血栓症の素因があると考えられた。入院時の血液検査でAT III，プロテインC活性，プロテインS活性はいずれも低下していたが，第22病日の再検査ではプロテインSのみが活性36%，抗原量46%と低値のままであった。入院時は広範な血栓形成により各分子が消費され低値を示したと考えられた。しかし，第19病日には可溶性フィブリンモノマーが正常化しており凝固活性状態は離脱したと考えられることから，第22病日のプロテインS活性の低下は異常であると判断した。また，患者家族も検査した結果，子3人中2人でプロテインS活性および抗原量が低下していたため，先天性プロテインS欠乏症と診断した。術直後よりヘパリン持続静注による抗凝固療法を開始し，急性期以降もワルファリン内服を継続し，血栓症の再発がみられることなく経過している。今回新たにプロテインS欠乏症が判明した患者家族に血栓症の既往はなく予防的な抗凝固療法は行っていないが，長時間の乗り物移動や手術による長期臥床など静脈血栓症発症のリスクが高い場合は抗凝固療法の開始を検討すべきと考えられた。 医学中央雑誌，PubMedを用いて検索した結果，我々が渉猟し得た範囲ではプロテインS欠乏症によるSMVTは計51例の症例報告がなされていた（Table 2）。男女比は44:7と男性に多く，37.3%に肺塞栓症や深部静脈血栓症などの血栓症の既往を認めた。51例中29例で初期治療として手術が選択され，そのうち8例でsecond look operationが施行されていた。ヘパリンおよびワルファリンによる抗凝固療法は51例全例で施行されていた。近年は画像診断の進歩により早期に診断可能となり，保存的治療のみで改善する例も増加している。抗凝固療法や血栓溶解療法の普及により死亡率も以前より低下している 16が，渉猟した51例では，保存的治療のみで改善した症例や血栓溶解療法を施行した症例の年代による増加あるいは低下といった変化はみられなかった。経過中の合併症は，小腸壊死によるイレウスが9例でみられ，全例で初期治療に保存的治療を選択していた。渉猟した51例のうち死亡例は1例のみであり，自験例のように経過中にCPAに至り蘇生した症例の報告はなかった。 SMVTに対する大量腸管切除による短腸症候群は予後不良因子であり 17，回避すべき合併症である。二期的手術に血栓溶解療法を組み合わせ，短腸症候群を回避した報告 18や，初期治療で血栓溶解療法を選択すると切除腸管が短縮した報告 19がある。今回，渉猟したプロテインS欠乏症によるSMVTで手術と血栓溶解療法を併用した症例は6例あり，いずれも短腸症候群の合併はなかった。また，短腸症候群を合併した3例は，いずれも初期治療に手術療法を選択されたが，血栓溶解療法は併用されていなかった。プロテインS欠乏症などの凝固異常を有する症例においても，血栓溶解療法を併用することで腸管を温存でき，短腸症候群を回避できる可能性があると考えられた。 今回，プロテインS欠乏症による上腸管静脈血栓症からCPAとなった1症例を経験した。CPAに対して速やかな蘇生処置に加え，緊急手術を行い，低体温療法および計画的なsecond look operationを組み込むことで救命することが可能であった。 CPAに至っても，蘇生処置に反応し短時間で自己心拍再開が得られた症例では，速やかな原因検索を行い，根本治療が可能な病態であれば，積極的に手術治療を行うことで救命できる可能性がある。 本稿のすべての著者に規定された利益相反はない。

The chain of survival in hypothermic circulatory arrest: encouraging preliminary results when using early identification, risk stratification and extracorporeal rewarming.

BackgroundThe prognosis in hypothermic cardiac arrest is frequently good despite prolonged period of hypoperfusion and cardiopulmonary resuscitation. Apart from protective effect of hypothermia itself established protocols of treatment and novel rewarming techniques may influence on outcome.The purpose of the study was to assess the outcome of patients with hypothermic circulatory arrest treated by means of arterio-venous extracorporeal membrane oxygenation (ECMO) according to locally elaborated protocol in Severe Accidental Hypothermia Center in Cracow, Poland.MethodsProspective observational case-series study – all patients with confirmed hypothermic cardiac arrest consulted with hypothermia coordinator were accepted for extracorporeal rewarming, unless contraindications for ECMO were observed (active bleeding).ResultsThe study population consisted of 10 patients (7 male, median age 48.5 years). The core temperature measured esophageally was 16.9–28.4 °C, median 22 °C. On admission 5 patients presented with asystole and 5 with ventricular fibrillation. Duration of circulatory arrest before ECMO implantation was 107 to 345 min (median 156 min). The duration of ECMO support was 1.5 to 91 h (median 22 h). Cardiorespiratory stability and full neurologic recovery was achieved in 7 patients. The duration of mechanical ventilation was 88–437 h (median 177 h) and the length of stay in the ICU was 8–26 days (median 15 days). All survivors had mildly impaired (1 patient, LVEF 40 %) or preserved (6 patients, LVEF 55–65 %) left ventricular systolic function at the time of discharge from ICU. The cause of death of non-survivors (three patients) was acute myocarditis, massive retroperitoneal bleeding, and massive gastrointestinal bleeding.Discussion and ConclusionsOur data confirm the high survival rate (70 %) and excellent neurologic outcome in hypothermic cardiac arrest. The following key elements seem to impact the final prognosis: the appropriate coordination of the rescue operation, immediate high-quality CPR (preferably using mechanical chest compression system) and application of ECMO for rewarming and cardiorespiratory support.

Blood pressure–targeted stepwise resuscitation of hemorrhagic shock in a swine model

BackgroundProlonged hemorrhagic shock and subsequent resuscitation frequently results in hemodynamic compromise. This study was designed to investigate the hemodynamic effect of the stepwise increase of blood pressure during initial resuscitation. Materials and methodsFifteen anesthetized male pigs (35 ± 5 kg) were used. Hemorrhagic shock was induced by losing 40% of estimated blood volume over 40 min and 10% of estimated blood volume over 20 min through the femoral artery and was maintained at a mean arterial pressure (MAP) of 30 ± 3 mm Hg for 2.5 h. The resuscitation of the rapid resuscitation (RR) group was targeted to reach MAP of 70 ± 5 mm Hg immediately by transfusion of shed blood via the femoral artery. The resuscitation of the pressure-targeted stepwise resuscitation (PSR) group was targeted to increase MAP by 10 mm Hg every 10 min up to 70 mm Hg, and then, the MAP was maintained at 70 ± 5 mm Hg until transfusion of the entire shed blood. ResultsDuring the initial resuscitation period of 30 min, the heart rate was significantly lower in the RR group than in the PSR group (P < 0.05), and mixed venous oxygen saturation was significantly higher in the RR group than in the PSR group during the 30 min of initial resuscitation (P < 0.05). After 2 h of resuscitation, cardiac output and stroke volume were significantly higher in the PSR group than in the RR group (P < 0.05), and the systemic vascular resistance was significantly lower in the PSR group than in the RR group (P < 0.05). ConclusionsA stepwise increase of blood pressure compared with rapid normalization improves hemodynamic parameters in the swine hemorrhagic shock model.

Sphingosine 1‐Phosphate (S1P) Attenuates Combined Acute Alcohol Intoxication and Hemorrhagic‐Shock/Resuscitation‐Induced Microvascular Hyperpermeability in Rat Mesentery

Alcohol intoxication‐related injuries remain a significant clinical problem involving at least 38 million individuals and producing and estimated $223.5 billion health care cost burden in the US. In the emergency room, intoxicated trauma patients present with increased injury severity and are more hypotensive, a predictor of poor outcomes. We have previously demonstrated that acute alcohol intoxication causes microvascular hyperpermeability in vivo, and also exacerbates hemorrhagic shock/resuscitation‐ (HSR)‐induced microvascular leakage. In the current study, we tested the hypothesis that the barrier‐enhancing bioactive lipid Sphingosine 1‐Phosphate (S1P) can reverse the microvascular hyperpermeability and hypotension following combined acute alcohol intoxication and HSR. Carotid artery, jugular vein, and indwelling gastric catheters were surgically placed in anesthetized Sprague Dawley rats. Following 6–7 days recovery, conscious, unrestrained rats received 2.5 g/kg alcohol via the intragastric catheter, followed by HSR (fixed pressure of 40 mm Hg for 1 h, followed by Lactated Ringers (LR), 40% i.v. bolus + 2x total blood volume removed infusion over 1 h). During resuscitation, the rats received 0.003, 0.03, or 0.1 mg/kg S1P within the LR fluid. Following the 1‐h resuscitation phase, the rats were anesthetized for intravital microscopy of the mesenteric microcirculation. FITC‐Albumin served as a tracer to determine extravasation, quantified by measuring integrated optical intensity (IOI) of the extravascular areas adjacent to postcapillary venules. The results show that by the end of the 1‐h fluid resuscitation period, the group receiving LR supplemented with 0.1 mg/kg S1P displayed significantly restored MAP compared to Alcohol/HSR (89.1 ± 3.6 mm Hg for Alcohol/HSR + 0.1 mg/kg S1P vs. 75.2 ± 3.1 mm Hg for Alcohol/HSR, p&lt;0.05). This trend persisted during the subsequent intravital microscopy phase of the experiment (86.3 ± 3.3 mm Hg Alcohol/HSR + 0.1 mg/kg S1P vs. 68.3 ± 4.3 mm Hg Alcohol/HSR, p&lt;0.05). In addition, 0.1 mg/kg S1P reduced the alcohol/HSR‐induced microvascular hyperpermeability by 50% (542.3 ± 58.4 IOI units for Alcohol/HSR + 0.1 mg/kg S1P vs. 1061.7 ± 142.1 IOI units for Alcohol/HSR, p&lt;0.001). These data show that fluid resuscitation augmented with 0.1 mg/kg S1P ameliorates alcohol/HSR‐induced hypotension and microvascular hyperpermeability more effectively than standard fluid resuscitation. Overall, the data show promise for using fluid resuscitation augmented with S1P for improving circulation in traumatic injury patients.Support or Funding InformationSupported by NIH grants R01HL098215 and R21AA020049, and the ABMRF/Foundation for Alcohol Research.

Delayed Graft Function Is Associated with Microvascular Thrombosis in a Donor with Disseminated Intravascular Coagulation

Microvascular thrombosis is an uncommon pathological finding in deceased donor kidneys. It is associated with disseminated intravascular coagulation (DIC) after brain injury in the donor. Although DIC in deceased kidney donors is known to have no association with graft outcome, microvascular thrombosis with DIC in a donor can cause renal graft impairment. For this reason, some transplantation centers do not accept these kidneys. A 39-year-old female donor had a subarachnoid hemorrhage. After a short period of cardiopulmonary resuscitation, we applied extracorporeal membrane oxygenation to maintain hemodynamic stability. The laboratory data were consistent with DIC. The recipient was a 38-year-old male patient who had been undergoing hemodialysis for 7 years because of end-stage renal disease of unknown cause. Zero-time graft biopsy revealed multiple intraluminal fibrin thrombi without peritubular capillaritis. Delayed graft function occurred after transplantation, and hemodialysis was started. Graft renal biopsy was performed on the third day after transplantation. The percentage of intraglomerular fibrin thrombi had decreased, and no significant peritubular capillaritis or C4d staining was observed. The function of the transplanted kidney started to recover, and hemodialysis was discontinued on the 10th day after surgery without specific treatment. Follow-up biopsy performed 20 days after the transplantation revealed normal kidney with completely resolved fibrin thrombi. We report herein a case of microvascular thrombosis in renal allograft from a DIC donor.