Temporizing surgical management improves outcome in patients with Vibrio necrotizing fasciitis complicated with septic shock on admission

burns 40 (2014) 446–454

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Temporizing surgical management improves outcome in patients with Vibrio necrotizing fasciitis complicated with septic shock on admission Guang-Liang Hong a,1, Xiao-Qin Dai b,1, Cai-Jiao Lu c, Jia-Ming Liu d, Guang-Ju Zhao a, Bin Wu a, Meng-Fang Li a, Zhong-Qiu Lu a,* a

Department of Emergency Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China b Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China c Department of Burns Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China d School of Environmental Science and Public Health, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China

article info

abstract

Article history:

Background: Necrotizing fasciitis (NF) caused by Vibrio infection is one of the most fatal

Accepted 9 August 2013

diseases, resulting in high morbidity and mortality. Early diagnosis and effective surgical intervention are the mainstays for better outcomes for affected patients. Currently, stan-

Keywords:

dard surgical management calls for prompt and aggressive debridement and amputation.

Vibrio necrotizing fasciitis

However, due to its rapid progression and deterioration, 50–60% of Vibrio NF cases present

Septic shock

with septic shock and multiple organ dysfunction on admission. These patients, who

Treatment

usually have many surgical contraindications, are unable to tolerate a prolonged aggressive

Surgical strategy

surgical debridement. Therefore, determining the optimal surgical intervention for these

Incision and drainage

particularly severe patients remains a formidable problem in emergency medicine.

Aggressive debridement

Methods: A retrospective study was conducted on patients who underwent surgery for Vibrio NF and septic shock on admission to the emergency room from April 2001 to October 2012. These patients received the same treatment protocol, with the exception of the initial surgical intervention strategy. Nineteen patients were treated with a temporizing strategy, which called for simple incisions and drainage under regional anesthesia, followed by complete debridement 24 h later. Another fifteen patients underwent aggressive surgical debridement during the first operative procedure. Basic demographics, laboratory results on admission, clinical course and outcomes were compared to assess the efficacy and safety of two initial surgical treatment methods: the temporizing strategy and the aggressive strategy. Results: Thirty-four patients were included in this study, and the average age was 51.65 years. Chronic liver disease was the most prevalent preexisting condition (50.00%) and the lower limbs were most commonly involved in infection (76.47%). In this patient population, 19 cases underwent surgery with a temporizing therapeutic strategy, while the remaining 15 cases were treated with an aggressive surgical strategy. There were no differences between

* Corresponding author at: Department of Emergency Medicine, The First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Lane, Lucheng District, Wenzhou 325000, Zhejiang, China. Tel.: +86 0577 86689751. E-mail addresses: [email protected], [email protected] (Z.-Q. Lu). 1 These authors contributed equally to this study. 0305-4179/$36.00 # 2013 Elsevier Ltd and ISBI. All rights reserved. http://dx.doi.org/10.1016/j.burns.2013.08.012

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the two groups with respect to demographics, severity of illness and laboratory data. Compared with those treated with the aggressive strategy, patients treated with the temporizing strategy had shorter operation time (40.79  16.61 vs. 102.00  18.97 min, p < 0.001), less bleeding (120.53  67.20 vs. 417.33  134.72 mL, p < 0.001), a reduced amount of intraoperatively administrated fluid (3144.70  554.71 vs. 1637.40  302.11 mL, p < 0.001), decreased maximum dose of dopamine (15.73  5.64 vs. 10.47  5.61 mg/kg/min, p = 0.011) and noradrenaline (20.13  7.50 vs. 13.37  6.18 mg/kg/min, p = 0.007), lower arterial lactate values at the end of surgery (5.56  1.99 vs. 8.66  3.25 mmol/L, p = 0.004), and, most importantly, lower mortality (26.32% vs. 60.00%, p = 0.048). All other treatment conditions, such as duration of vasopressor therapy, number of debridement procedures, rate of amputation, ICU length of stay and hospital length of stay, were the same for both groups. Conclusion: The temporizing strategy, with early initiation of simple incisions and drainage under regional anesthesia followed by complete debridement 24 h later, is more feasible and effective for patients with Vibrio NF complicated with septic shock, as compared with the aggressive surgical debridement strategy. # 2013 Elsevier Ltd and ISBI. All rights reserved.

1.

Introduction

Necrotizing fasciitis (NF), a rapidly progressive soft tissue infection, is a rare but life-threatening condition that can lead to septic shock, multiple organ dysfunction, and even death in some circumstances. Vibrio NF is generally associated with the consumption of raw sea food or exposure to sea water by individuals with chronic liver disease or in an immunocompromised state. Previous reports have shown that Vibrio NF is more hazardous than other kinds of necrotizing fasciitis [1–3]. Despite the existence of advanced antibiotics and infection control practices, the mortality rate of these patients is higher than 40–60%, and can approach 90% when complicated with shock on initial presentation [4]. Early diagnosis and effective surgical intervention are the strategies for better outcomes for Vibrio NF patients. Standard surgical management dictates the immediate and complete debridement of necrotic tissue, including amputations in medically unstable patients [5,6]. Researchers reported that inadequate debridement is associated with a seven-fold increase in death from this disease [7], while a delay in operation is associated with a nine-fold greater likelihood of death [8]. However, no quantifiable methods have been reported to define adequate debridement and determine the extent of resection during the initial operative procedure [9]. Furthermore, it is difficult to distinguish infected fascia from uninfected fascia during the first operation in elderly and critically ill patients with extensive edema [10]. Thus, the initial radical surgery is a time-consuming and labor-intensive procedure with extensive blood loss, which possibly worsens the physiological upset and causes rapid deterioration of some critical patients such as those with septic shock and multiple organ dysfunction. Unfortunately, due to its rapid progress, 50–60% of Vibrio NF patients present with septic shock and multiple organ dysfunction on initial presentation to the hospital [11,12]. These septic shock patients usually have surgical contraindications such as hypotension, lactic acidosis, severe coagulation disorders and thrombocytopenia. In these cases, general anesthesia and lengthy and extensive surgical

debridement will be poorly tolerated during the first hours after presentation [13]. Therefore, the optimal surgical interventions for these particularly severe patients with Vibrio NF should obviously be evaluated on a patient-to-patient basis, which remains a formidable task in emergency medicine. In the present study, we developed a temporizing surgical strategy for treating these critically unstable patients with Vibrio NF and septic shock. Early initiation of surgical treatment with simple incision and drainage under regional anesthesia, followed by complete debridement 24 h later, was used as a substitute for aggressive surgical debridement and amputation during the first operative procedure. We retrospectively analyzed 34 patients who underwent surgery for Vibrio NF complicated with septic shock on admission to emergency room, and compared the efficacy and safety of the temporizing surgical treatment strategy with the aggressive strategy.

2.

Patients and methods

2.1.

Patients

We carried out a retrospective medical record review of patients who underwent surgery for NF caused by Vibrio infection from April 2001 to October 2012 at the First Affiliated Hospital of Wenzhou Medical University, a tertiary hospital with bed capacity of 2000 and serving approximately 13 million people. The Institutional Review Boards at the First Affiliated Hospital of Wenzhou Medical University approved this study.

2.2.

Inclusion criteria

We included all patients who underwent surgery for Vibrio NF with septic shock on initial presentation. (1) All cases met the following criteria for early clinical diagnosis of vibrio NF: (a) disease onset between April and November; (b) presentation of acute fever, accompanied with characteristic skin and muscle impairment, with rapid progression to the whole body; (c) presentation of hypotension or shock within 48 h, followed by

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rapid development of MODS; and (d) medical history of longterm ethanol abuse or chronic liver diseases. Supporting evidence included living along the coastal areas, consumption of raw seafood within one week, and exposure to seawater with limb wounds or punctures caused by marine delicacies. (2) Vibrio infection was confirmed by isolating pathogenic bacteria from soft-tissue lesions and/or blood collected immediately after arrival at the emergency department. (3) Necrotizing soft-tissue infection was defined by either histopathologic or surgical findings such as the presence of necrosis of skin, subcutaneous fat, superficial fascia, or underlying muscles. (4) The diagnosis of septic shock was based on a revised consensus guideline established in 2001 [14]. All patients received the same treatment protocol, with the exception of the initial surgical intervention strategy.

2.3.

Surgical treatment

2.3.1.

Indications of initial operation

Indications for initiation of surgical treatment in the emergency room were the same as we reported previously [15]. Briefly, emergent surgical intervention was explored immediately for patients presenting with signs of local damage (rapidly progressive swelling, dissymmetric pain, ecchymosis, blood blister, skin necrosis and subcutaneous crepitation, etc.) combined with systemic toxemic symptoms and abnormal laboratory results (increased LRINEC score [16] and creatine phosphate kinase value).

2.3.2.

Aggressive surgical strategy for initial operation

Once a patient met the indications for initial operation, the aggressive surgical debridement was performed within 1–2 h irrespective of the patient response to resuscitation attempts. The anesthesiologist plays a critical role in this endeavor because continued resuscitative efforts are made intraoperatively. In the state of general anesthesia, the patients underwent wide, extensive debridement of all tissues that could be easily separated from the deep fascia with gentle finger dissection (Fig. 1A). The extent of resection was based on clinical judgment and influenced by the gross appearance of the tissues involved. The absence of inflammation and purulence, the presence of normal bleeding at the line of incision, and the contractility of viable muscle were used to judge the adequacy of debridement. Electrocoagulation was performed to prevent bleeding and in some cases a gelatin sponge was very useful for the errhysis of the wounds.

2.3.3.

Temporizing surgical strategy for initial operation

In contrast with the aggressive surgical debridement of necrotic tissue, this management strategy calls for incisions and drainages, which were mostly performed with regional anesthesia by peripheral nerve blocks on the affected limbs during the first operative procedure, and was followed by complete debridement 24 h later. It was used as a temporizing therapeutic strategy for the patients with NF and septic shock. Signs of local damage, such as ecchymosis and blood blisters, were always used to indicate the appropriate location for incision. Employing this as the center, we gradually extended the incision, bluntly separating the subcutaneous tissues, and cutting open fascia and sarcolemma, which was strongly

Fig. 1 – Surgical strategies for initial operation in patients with vibrio NF complicated with septic shock on admission. (A) Aggressive debridements was used for a case with NF caused by Vibrio alginolyticus infection involved the right upper limb. (B) Multiple small incisions was performed for a patient who was diagnosed with Vibrio vulnificus NF on the right lower extremity and confirmed with severe coagulation disorders. (C) Single large incision was selected for a Vibrio vulnificus NF with limited lesion on the right lower extremity and good blood coagulation.

based on the wound of the affected limbs. As we previously reported [15], according to the local conditions and the tension of the extremities two operational patterns could be selected: (1) multiple small incisions (Fig. 1B); and (2) single large incision (Fig. 1C). The former procedure was performed in cases of a wide-ranging lesion on the extremities with poor blood coagulation and high tension, and with intact healthy skin and soft tissue. The later measure was chosen for patients

burns 40 (2014) 446–454

with a limited lesion of the extremities with good blood coagulation and low tension. The goals of the initial operation were to decompress the limbs and improve perfusion and drainage of the extremities. Once these goals were reached, the operation was finished in a timely manner. The wound surface was then protected by bandage dressing after being washed successively with 3% hydrogen peroxide solution, physiological saline and 2.5% iodophor. This procedure, which is easier and faster to perform than the aggressive surgical intervention, was completed within 1–2 h after the diagnosis was suspected or established during fluid resuscitation. After the emergency incision and drainage were performed, patients were admitted to EICU and continued comprehensive efforts, including resuscitation with the EGDT (early goaldirected therapy) protocol, anti-bacterial treatment, correction of physiological disorders correction and supportive care, were carried out to stabilize the patients’ condition. These patients were returned to operating room for complete debridement 24 h later.

2.3.4. Continued treatment of wound surface after initial operation After the initial surgical treatment (either the temporizing or aggressive strategy), the wounds were re-evaluated every 24 h when changing the wound dressing. Repeated debridement was performed as needed. Finally, an autogenous skin graft was applied to repair the wound surface for the majority of patients. For some cases with obvious muscle necrosis that obviated restoration and reconstruction, amputation was undertaken.

2.4.

Recorded items

A computerized spreadsheet (Microsoft Excel 2003) was generated for this study and included the following variables: age, gender, pre-existing medical conditions (such as chronic liver diseases, diabetes, hypertension, chronic renal failure, etc.), vital signs on admission (including mean arterial pressure (MAP), heart rate (HR) and rectal temperature), basic laboratory values and laboratory risk indicator for necrotizing fasciitis (LRINEC) score on admission, acute physiology and chronic health evaluation II (APACHE II) score and sequential organ failure assessment (SOFA) score for the first 24 h, infection site, clinical stage of NF at diagnosis [17], pathogenic organism(s), time from emergency department arrival to initial operation, operation duration, intraoperative blood loss, intraoperative fluid resuscitation and vasopressor therapy, use of a ventilator and continuous renal replacement therapy (CRRT), ICU length of stay, hospital length of stay, and hospital mortality.

2.5.

Statistical analysis

Continuous variables are expressed as mean  SD, and the student’s t-test was used for comparison of continuous data. Categorical data were compared using chi-square tests. A differenced with a two-tailed p value <0.05 was considered statistically significant. Statistical Package for the Social Sciences software (SPSS, version 16.0) was used for data analysis.

3.

Results

3.1.

Characteristics of the study patients

449

We included all 34 patients who underwent surgery for Vibrio NF with septic shock on initial presentation between April 2001 and October 2012. These cases included 29 cases of Vibrio vulnificus infection, 3 cases of Vibrio alginolyticus infection and 2 cases of V. alginolyticus infection (Table 1). All the patients were adults and the study population had an average age of 51.65 years, with most of them (82.35%) male. Chronic liver disease was the most prevalent preexisting condition in the study cohort, and was present in half of the patients (n = 17, 50.00%). Other medical comorbidities observed included diabetes mellitus (23.53%), hypertension (23.53%), chronic renal failure (14.71%), and malignancy (8.82%). Twelve patients (35.29%) had no identifiable risk factors. The lower limbs were most common area of infection (accounting for 76.47%), followed by the upper extremities and back (Table 1). No patients appeared to have compartment syndrome although it has been reported in patients with Vibrio NF. Nineteen of the cases in this study underwent surgery for NF with the temporizing therapeutic strategy, while the remaining 15 cases were treated with the aggressive surgical strategy. At baseline, there were no differences between the two groups with respect to general characteristics and severity of illness (Table 1). Laboratory data (Table 2) showed that most patients presented with obvious lactic acidosis (91.18%), coagulation disorders (85.29%), and renal dysfunction (79.41%) on admission. Further, more than half of the study population presented with thrombocytopenia (58.82%), anemia (52.94%), impaired liver function (52.94%) and hyponatremia (61.76%) on admission. The mean LRINEC score was only 4.82  2.38 in the study population. However, all laboratory parameters, including LRINEC score, were not statistically different between patients with temporizing and aggressive surgical treatment (Table 2).

3.2.

Management of shock during the initial operation

Table 3 shows the clinical course during the time of initial surgical treatment. All the patients in the temporizing therapy group underwent surgery with regional anesthesia, with the exception of two patients who were intubated due to impaired oxygenation during the surgery and were treated with a combination of regional and general anesthesia. All the patients in the aggressive therapy group were managed with general anesthesia. The mean interval between admission and initial operation was 75.88 min for the whole study population, and this parameter was similar between the temporizing strategy group and the aggressive strategy group. However, the average procedure time was significantly shorter in patients that underwent temporizing operative treatment as compared with those who were initially treated with the aggressive surgical strategy (40.79  16.61 vs. 102.00  18.97 min, p < 0.001). The patients in the temporizing operative group also experienced less bleeding during the initial operation (120.53  67.20 vs. 417.33  134.72 mL, p < 0.001). Although the minimum CVP and MAP during the operation

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Table 1 – Comparison of basic demographics between patients treated with temporizing and aggressive surgical strategy for initial operation.

Age (yr), mean  SD Gender, Males:females MAP on admission (mmHg), mean  SD HR (bpm), mean  SD Rectal temperature (8C) mean  SD Pre-existing disease, n (%) Chronic liver disease Diabetes mellitus Hypertension Chronic renal failure Malignancy Othera None APACHE II score, mean  SD SOFA score, mean  SD Site of infection, n (%) Lower extremities Upper extremities Back Clinical stage of NF at diagnosis, n (%) Stage 1 Stage 2 Stage 3 Pathogenic organisms, n (%) Vibrio vulnificus Vibrio alginolyticus Vibrio alginolyiicus

All patients (n = 34)

Patients with temporizing strategy for initial operation (n = 19)

Patients with aggressive strategy for initial operation (n = 15)

p

51.65  13.56 28:6 60.32  6.64 112.59  17.85 36.91  2.20

50.79  12.99 16:3 61.37  6.67 113.32  20.56 36.64  2.74

52.73  14.65 12:3 59.00  6.58 111.67  14.34 37.25  1.24

0.685 1.000 0.309 0.794 0.433

17(50.00) 8(23.53) 8(23.53) 5(14.71) 3(8.82) 1(2.94) 12(35.29) 29.91  8.99 14.61  3.92

10(52.63) 5(26.32) 4(21.05) 2(10.53) 1(5.26) 1(5.26) 5(26.32) 29.79  8.70 14.79  3.81

7(46.67) 3(20.00) 4(26.67) 3(20.00) 2(13.33) 0(0.00) 7(46.67) 30.07  9.65 14.40  4.19

0.730 1.000 1.000 0.634 0.571 1.000 0.218 0.931 0.779

26(76.47) 6(17.65) 2(5.88)

15(78.95) 2(10.53) 2(10.53)

11(73.33) 4(26.67) 0(0.00)

1.000 0.370 0.492

5(14.71) 6(17.65) 23(67.64)

3(15.79) 2(10.53) 14(73.68)

2(13.33) 4(26.67) 9(60.00)

1.00 0.370 0.475

29(85.29) 3(8.82) 2(5.88)

16(84.21) 1(5.26) 2(10.53)

13(86.67) 2(13.33) 0(0.00)

1.000 0.571 0.492

SD, standard deviation; MAP, mean arterial pressure; HR, heart rate; APACHE, acute physiology and chronic health evaluation; SOFA, sequential organ failure assessment. a A case with rheumatic arthritis and history of taking cortisone.

were not different between the temporizing strategy group and the aggressive strategy group, the amount of intraoperatively administrated fluid (3144.70  554.71 vs. 1637.40  302.11 mL, p < 0.001) and maximum dose of intraoperative vasopressor therapy (dopamine and noradrenaline) were both markedly higher in patients with aggressive surgical debridement than those that had undergone the temporizing operative procedure. Notably, even though the arterial lactate levels were the same for both groups before the treatment, the arterial lactate value at the end of surgery was obviously lower in patients that underwent the temporizing surgical strategy than that in patients with aggressive surgical debridement (5.56  1.99 vs. 8.66  3.25 mmol/L, p = 0.004). No patients returned to the operation room before 24 h after the initial procedure for both groups.

3.3.

about 6 days and the mean hospital length of stay was 24.59 days. The patients that underwent the temporizing surgical procedure had a slightly longer inpatient stay than the aggressively treated patients, but this was not found to be statistically significant ( p = 0.196). Fourteen patients (41.18%) had died by the end of data collection, with 5 deaths (26.32%) in the temporizing strategy group and 9 deaths (60.00%) in the aggressive strategy group, and there were no significant differences in the mortality rate of these patients among different time periods (data not shown). Notably, the mortality rate was significantly lower in patients who were treated with the temporizing surgical strategy compared with those that underwent aggressive operative treatment ( p = 0.048).

4.

Discussion

Outcomes of the study patients

Table 4 depicts the data concerning the main outcomes in these patients. The difference in mean time to withdrawal of vasopressor therapy between the two groups did not reach statistical significance ( p = 0.216). The average number of surgical debridement procedures (3.05  1.31 vs. 2.80  1.57, p = 0.612) and the proportion of amputations (10.53% vs. 20.00%, p = 0.634) were both similar between the two groups. For the study population, the mean ICU length of stay was

Vibrio NF, which occurs frequently in individuals with chronic liver disease, diabetes or in an immunocompromised state, is a rare but fatal disease resulting in high morbidity and mortality. Numerous studies on NF have been published recently, and some points of agreement in the literature include the difficulty of diagnosis, the importance of early diagnosis and surgical treatment, and the better outcome realized with aggressive surgical debridement of necrotizing tissue [7,8,18]. However, the rapid progression

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Table 2 – Comparison of baseline laboratory measurements on admission between patients treated with temporizing and aggressive surgical strategy for initial operation.

WBC (109/L), mean  SD Abnormal WBC, n (%) WBC >25(109/L), n (%) Hg (g/L), mean  SD Anemia (Hg < 110), n (%) Platelets (109/L), mean  SD Thrombocytopenia (platelets<50), n (%) PH values, mean  SD Uncompensated acidosis (PH < 7.35), n (%) PO2 (mmHg), mean  SD PO2 < 80, n (%) PCO2 (mmHg), mean  SD PCO2 <25 mmHg, n (%) BE (mmol/L), mean  SD PT(s), mean  SD Abnormal PT, n (%) INR, mean  SD Glucose (mmol/L), mean  SD Na values (mmol/L), mean  SD Hyponatremia (Na<135), n (%) K values (mmol/L), mean  SD Creatinine (mmol/L), mean  SD Abnormal creatinine, n (%) Arterial lactate (mmol/L), mean  SD Lactate  4 mmol/L, n (%) C-reactive protein (mg/L), mean  SD CPK (m/L), mean  SD TBIL (mmol/L), mean  SD Abnormal TBIL, n (%) Albumin (g/L), mean  SD LRINEC score, mean  SD LRINEC score  6, n (%)

All patients (n = 34)

Patients with temporizing strategy for initial operation (n = 19)

Patients with aggressive strategy for initial operation (n = 15)

p

14.12  8.89 24(85.87) 5(14.71) 110.01  20.11 18(52.94) 82.50  101.60 20(58.82) 7.35  0.07 12(35.29) 107.83  38.84 10(29.41) 26.17  6.48 15(44.12) 8.59  4.68 20.56  4.74 29(85.29) 1.85  0.61 6.99  3.17 133.15  4.96 21(61.76) 3.84  0.98 168.50  92.67 27(79.41) 8.14  2.59 31(91.18) 68.4  60.29 2038.6  3311.17 57.09  37.21 18(52.94) 26.54  4.48 4.82  2.38 11(32.35)

13.95  8.29 13(68.42) 2(10.51) 110.12  20.44 9(47.37) 58.63  63.10 13(68.42) 7.35  0.06 7(36.84) 111.79  36.88 6(31.58) 25.31  5.39 9(47.37) 8.91  4.33 20.77  4.33 17(89.47) 1.94  0.60 6.62  2.23 132.42  4.60 13(68.42) 3.94  0.99 150.00  88.73 14(73.68) 8.02  2.32 18(94.74) 78.42  52.34 1784.90  2809.92 58.03  33.00 10(52.63) 25.83  4.67 4.37  1.42 5(26.16)

14.35  9.89 11(73.33) 3(20.00) 109.87  20.40 9(60.00) 112.73  132.14 7(46.67) 7.36  0.08 5(33.33) 102.81  41.95 4(26.67) 27.27  7.69 6(40.00) 8.19  5.21 20.29  5.35 12(80.00) 1.74  0.63 7.47  4.11 134.07  5.39 8(53.33) 3.70  0.97 191.93  95.22 13(86.67) 8.28  2.97 13(86.67) 56.93  69.05 2359.90  3936.23 55.75  44.03 8(53.33) 27.53  4.19 5.40  3.36 6(40.00)

0.899 1.000 0.634 0.972 0.464 0.125 0.201 0.710 1.000 0.512 1.000 0.387 0.667 0.664 0.774 0.634 0.333 0.446 0.344 0.369 0.482 0.195 0.426 0.777 0.571 0.309 0.623 0.874 0.968 0.324 0.280 0.475

Hg, hemoglobine; BE, base excess; PT, prothrombin time; INR, internal normalized ratio; CPK, creatine phosphate kinase; TBIL, total bilirubin; SD, standard deviation; LRINEC score, laboratory risk indicator for necrotizing fasciitis score. Normal values were defined as WBCs (4–10  109/ L), platelets (100–300  109/L), pH (7.35–7.45), Na (135–145 mmol/L), K (3.5–4.5 mmol/L), creatinine (53–106 mmol/L) and TBIL (3.4–17.1 mmol/L).

Table 3 – Management of shock during the initial operation in patients with temporizing or aggressive strategy. All patients (n = 34) 75.88  28.72 Time from admission to initial operation (min), mean  SD Mode of anesthesia, n (%) Regional anesthesia 17(50.00) 15(44.12) General anesthesia 2(5.88) Combination of regional and general anesthesia Procedure time (min), mean  SD 67.79  35.42 251.47  180.38 Intraoperative blood loss (mL) mean  SD 2302.40  870.30 Intraoperative fluid therapy (mL), mean  SD Intraoperative vasopressor therapy (type and maximum) Dopamine (mg/kg/min), mean  SD 12.79  6.14 16.35  7.51 Noradrenaline (mg/kg/min), mean  SD Intraoperative monitoring Minimum of CVP (mmHg), mean  SD 8.79  2.86 65.76  7.18 Minimum of MAP (mmHg), mean  SD 6.93  3.01 Arterial lactate (mmol/L), mean  SDa

Patients with temporizing strategy for initial operation (n = 19)

p

71.05  23.78

82.00  33.85

17(89.47) 0 2(10.53)

0 15(100.00) 0

40.79  16.61 120.53  67.20 1637.40  302.11

102.00  18.97 417.33  134.72 3144.70  554.71

10.47  5.61 13.37  6.18

15.73  5.64 20.13  7.50

0.011 0.007

8.58  2.61 67.42  7.21 5.56  1.99

9.07  3.21 63.67  6.80 8.66  3.25

0.629 0.132 0.004

CVP, central venous pressure; MAP, mean arterial pressure; SD, standard deviation. Blood samples were taken within half an hour after surgery.

a

Patients with aggressive strategy for initial operation (n = 15)

0.276

<0.001 <0.001 <0.001

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Table 4 – Comparison of outcomes between patients treated with temporizing and aggressive surgical strategy for initial operation.

Time to withdrawal of vasopressor therapy (days) mean  SD Total number of operative debridements, mean  SD Amputation, n (%) ICU stay (days), mean  SD Hospital stay (days), mean  SD Hospital mortality, n (%)

All Patients (n = 34)

Patients with temporizing strategy for initial operation (n = 19)

Patients with aggressively strategy for initial operation (n = 15)

3.44  3.15

4.04  3.06

2.68  3.20

0.216

2.94  1.41

3.05  1.31

2.80  1.57

0.612

5(14.71) 6.63  3.71 24.59  18.65 14(41.18)

2(10.53) 7.24  2.96 29.84  17.77 5(26.32)

3(20.00) 5.87  4.85 17.93  18.14 9(60.00)

0.634 0.318 0.064 0.048

p

SD, standard deviation.

and deterioration of Vibrio NF often cause patients to present with septic shock and MODS on admission, which leads to many contraindications and high risks for general anesthesia and extensive surgical treatment. Despite the severity of this disease, these patients have not been extensively studied as a distinct population in the literature. Therefore, the optimal initial surgical protocol for these hemodynamically unstable patients remains largely undefined. The present study included only severely ill patients who presented with Vibrio NF and septic shock on admission. And we focused on the efficacy and safety of a new surgical protocol, a temporizing strategy of initial treatment with simple incision and drainage under regional anesthesia followed by complete debridement 24 h later, and compared this strategy with initial surgery involving aggressive debridement. The 34 cases examined here were in critical condition and had various surgical contraindications, including unstable hemodynamic status (100%), marked lactic acidosis (91.18%), coagulation disorders (85.29%) and severe thrombocytopenia (58.82%). The mortality rate of the group of patients that underwent the aggressive surgical strategy was 60.00%, which falls within the wide range of mortality rate that had been reported in the last few years. A clinical study including 63 cases by Liu et al. [19] reported a mortality rate of 47.7% (21/44) for the subgroup of septic shock patients with NF caused by V. vulnificus when extensive and complete surgical operation was performed. A similar approach was used by Tsai et al. [20] and H’ng et al. [21], where mortality rates for the subgroup of septic shock patients with Vibrio NF were 41.5% and 50%, respectively. In a recent study conducted by Chen et al. [12], the mortality rate even reached 70.6% (24/34) when the aggressive surgical approach was applied. In contrast, in the present study, mortality was significantly reduced when the patients were treated with the temporizing surgical protocol (26.32%, p = 0.048). The clinical data acquired during the initial operation points to some possible explanations for this finding. First, all patients treated with the temporizing surgical protocol, with the exception of two, underwent surgery with regional anesthesia, which has few hemodynamic effects, whereas general anesthesia in patients treated with the aggressive surgical protocol can lead to a high risk of aggravation of hypotension and organic hypoperfusion [13,22]. In present study, although the minimum MAP during the operation between the two groups was not statistically different, the patients in the aggressive surgery group

appeared to benefit from more vasopressor therapy, which was reported to be associated with increased mortality [23]. In addition, several advantages were associated with the temporizing surgical protocol, including effective decompression and drainage as well as short duration, less blood loss and little physiologic insult. According to the latest sepsis management guide [24], the effective intervention associated with the least physiologic insult was recommended for severely septic patients when source control was indicated. The selection of the optimal source control method must weigh its benefits and risks and should be heavily based on the specific clinical situation. In present study, we separated the initial aggressive surgery protocol into two parts: initiation with simple incision and drainage, followed by complete debridement 24 h later. This course of treatment allowed the patients earlier access to EICU and more effective resuscitation. Although no difference was observed in the duration of vasopressor therapy between the two groups, the lower arterial lactate values at the end of surgery indicated better effects on early resuscitation in patients undergoing the temporizing surgical strategy. This finding highlights the advantage of the temporizing surgical strategy for the treatment of septic shock patients with NF caused by Vibrio infection. Amputation is supposed to be performed for medically unstable patients or for patients for whom re-exploration revealed progression of infection in an extremity [5]. The need for amputation has been reported to range from 25% to 50% for patients with extremity-based infections [25]. However, this disabling procedure is often difficult for the patients and their families to accept, both physically and psychologically, in the emergency clinical setting. Furthermore, the long-term outcomes of major amputations have been described with 5-year survival rates of 30–40% [26]. In present study, amputations were avoided in the first emergency operation, and only 5 patients, accounting for 14.71% of the entire study population, underwent this procedure. The amputation rate was even lower (10.53%) for patients that underwent the temporizing surgical strategy. This surgical approach, combined with later debridement and skin grafting, could thus maintain the integrity of the patient’s limbs and consequently improve the prognosis of the patients. The LRINEC score is one of the most popular scoring systems for identifying NF based on laboratory parameters. A LRINEC score of 6 is highly indicative of necrotizing fasciitis,

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with a 92% positive predictive value and a 96% negative predictive value [16]. However, in present study, only 11 patients (32.35%) had a LIRNEC score over 6, suggesting the unsuitability of this scoring system for Vibrio NF. Similar results were reported by Tsai et al. in a study of 70 cases of Vibrio NF [20]. There are some possible explanations for this finding. Vibrio NF often involves patients with chronic liver diseases (and was present in 50.00% of cases in this study), and these patients are often have impaired synthesis of c-reaction protein, which is an important component of the LRINEC scoring system. In addition, leucopenia is common in patients with chronic liver diseases and hypersplenism. Even in the face of acute infection, the white blood cell count was probably not increased in these cases, which contributes to a low LRINEC score. Our study has several limitations that warrant further investigation of the temporizing strategy. First and most importantly, it is limited by its retrospective design, and is based primarily on information obtained from an acute care surgery registry and chart review. As such, the data available are limited and subject to bias. A prospective randomized placebo-controlled clinical trial to determine its safety and efficacy is theoretically necessary but practically impossible due to the high lethality of this disease. In addition, the small number of patients limits the statistical validity of these findings. Finally, the findings are from a single medical institution and may not be applicable to all patient populations. In conclusion, this study supports the safety and effectiveness of the temporizing approach for the surgical management of Vibrio NF complicated with septic shock on admission as compared with aggressive surgery. Additionally, the temporizing approach may have the benefit of lower hospital mortality.

Conflict of interest statement The authors have no commercial associations or sources of support that might pose a conflict of interest.

Acknowledgements Supported by the grant of Key Construction Academic Subject of Zhejiang Province (11-CX26), Key Construction Academic Subject of Zhejiang Province (2012-XK-A28) and the Key Discipline Construction project of Colleges and Universities in Zhejiang Province.

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