Electrical nerve stimulation is an established method for localising nerves when performing lower extremity peripheral nerve blocks1; however, ultrasound-guided regional anaesthesia is becoming increasingly popular.2,3 For blockade of the sciatic nerve, some authors have not reported differences in the qualities of block for ultrasound and electrical nerve stimulation-guided techniques.4 Other investigators, however, have reported higher success rates with ultrasound-guided sciatic nerve blocks,5,6 and some recommend the combination of ultrasound and nerve stimulation to improve the quality of the block.7 An aspect rarely mentioned when discussing the issues of electrical nerve stimulation vs. ultrasound-guidance is the increase of the electrical stimulation threshold in patients with peripheral neuropathy, which could have a negative impact on the identification of the nerve. Bigeleisen et al. 8 observed a higher stimulation threshold in seven diabetic patients compared to non-diabetic patients when performing supraclavicular block. Only a few case reports have been published indicating an alteration of the motor response of the sciatic nerve to electrical stimulation in patients at risk of peripheral neuropathy.9–12 A systematic evaluation as to whether the electrical stimulation threshold for a motor response of the sciatic nerve is substantially increased in diabetic patients has not been carried out before.
Diabetic foot disease is a potentially disabling and life-threatening complication that affects up to 25% of patients with diabetes mellitus.13 It has been estimated that diabetic foot disease requires a major or minor amputation in approximately one quarter of patients.13 These patients represent a high-risk cohort frequently suffering from diabetic neuropathy.14 The question as to whether the motor stimulation threshold of the sciatic nerve is increased in these patients should be of substantial clinical relevance when using electrical nerve stimulation. We, therefore, examined this issue in patients undergoing surgery for diabetic foot gangrene and compared this to a cohort of non-diabetic patients, displaying no risk factors for neuropathy, who were undergoing orthopaedic surgery of the foot or ankle.
The study was designed as a prospective observational two-centre study with two parallel groups. The protocol of the study complied with the Declaration of Helsinki, was registered in the German Clinical Trial Register (DRKS00003255) and was approved by the Ethics Committee of the University of Freiburg (Ethical Committee Number 275/11, Chairperson Professor Dr S. Pollak) on 26 August 2011.
All patients provided written informed consent. We enrolled 30 patients with diabetes mellitus scheduled for surgical treatment of diabetic foot gangrene, and 30 non-diabetic patients undergoing orthopaedic foot or ankle surgery. Exclusion criteria were age lower than 40 years, pregnancy and infection of the upper thigh precluding the performance of a lateral sciatic nerve block. Further exclusion criteria for the non-diabetic patient group were end-stage renal disease, a history of central or peripheral nerve disease and neuromuscular disease. All patients were premedicated with temazepam 10 to 20 mg orally and underwent routine monitoring (Intelli-Vue MP70; Philips Medical Systems, Boeblingen, Germany) using ECG, pulse oximetry and non-invasive blood pressure measurement. A peripheral intravenous cannula was also inserted.
The sciatic block was performed in the supine position using a lateral approach, as described previously.15,16 The lower part of the leg to be blocked was placed on a 30-cm high support pillow. After cleaning the skin with an antiseptic solution, the sciatic nerve was identified with a high-frequency linear array transducer which was covered in a sterile sleeve and positioned at the posterior aspect of the thigh about 10 cm proximal to the popliteal fossa. Local anaesthetic was infiltrated subcutaneously at the needle insertion site between the tendons of the vastus lateralis and biceps femoris muscles. A stimulating needle (Stimuplex D Plus; Braun Melsungen AG, Melsungen, Germany) was connected to the nerve stimulator (Stimuplex HNS 12, Braun Melsungen AG) and the injection line was primed with local anaesthetic. The stimulating needle was directed under ultrasound guidance using an in-plane approach towards the lateral component of the sciatic nerve with the nerve stimulator set at 1.0 mA, a pulse width of 0.1 ms and a stimulation frequency of 1 Hz. When a typical motor response of the peroneal nerve (dorsiflexion or eversion of the foot) was obtained, the ultrasound picture was stored and the distance between needle tip and nerve was determined (secondary outcome). The needle was then advanced further, using ultrasound guidance without electrical stimulation, until the needle tip was located directly adjacent to the peroneal component of the sciatic nerve, which was displaced by gentle needle movements. The minimum current intensity to elicit a motor response of the peroneal nerve was determined (primary outcome). The measurements were confirmed by the anaesthetic assistant and a second anaesthetist. Subsequently, the local anaesthetic solution (equal parts of prilocaine 10 mg ml−1 and ropivacaine 7.5 mg ml−1) was injected after negative aspiration. The correct position of the needle was verified by observing the spread of the local anaesthetic around the nerve, indicating an extraneural injection. The needle was redirected to the dorsal and ventral sides of the sciatic nerve and local anaesthetic was incrementally injected up to a total dose of 30 to 40 ml. Dependent on the clinical circumstances and the decision of the anaesthetist, the saphenous nerve was blocked, either at the thigh behind the sartorius muscle under ultrasound control, or subcutaneously below the knee or above the medial malleolus. After completion of the nerve block, the patients received sedation with propofol 50 to 200 mg h−1 as clinically required. Surgery was started 30 to 45 min after completion of the nerve block. When the blockade was incomplete and not sufficient for surgery, anaesthesia was supplemented with analgesic drugs, such as opioids or low-dose ketamine.
Statistical analysis was performed using IBM SPSS Statistics 20 (IBM Corporation, Armonk, New York, USA). The data were checked for normal distribution by visual assessment of histograms and q–q plots. The data that adhered to a normal distribution are reported as mean (SD), otherwise as median (interquartile range). The data of the minimal stimulation threshold were normally distributed after logarithmical transformation and are reported as geometric means with 95% confidence interval (CI). The frequency of categorical variables was analysed using Fisher's exact test. Continuous data were compared by parametric (Student's two sample t-test) or non-parametric (Mann–Whitney U-test) tests, as appropriate. All tests were performed as two-sided tests with a significance level of P < 0.05.
Sample size calculation
The minimal required sample size was determined using the software G*Power (Department of Experimental Psychology, Heinrich-Heine-University, Düsseldorf, Germany).17 We estimated the required sample size in view of previous studies which revealed a stimulation threshold of the sciatic nerve of 0.32 (0.10) mA and of 0.42 (0.12) mA, respectively.18,19 We assumed that a doubling of the previously reported threshold would be of major clinical interest, as it corresponds with a threshold current of 0.6 to 0.8 mA, which distinctly exceeds the stimulation threshold to elicit a motor response (0.2 to 0.5 mA) recommended for peripheral nerve blockade.20 Due to these considerations, we calculated that a minimum sample size of 25 patients per group would be required to detect an increase of the stimulation threshold to 0.6 mA, assuming an SD of 40% of the stimulation threshold, which corresponds with an effect size of 0.8 with a two-sided α value of 0.05 and a β value of 0.2. Based on this estimated sample size, we enrolled 30 participants in each patient group to allow for patient drop-out.
All participants completed the study. Patient characteristics are reported in Table 1. Twenty-nine patients in the diabetic group had type 2 diabetes mellitus, and one patient had type 1. Fifteen diabetic patients required insulin therapy. Minor amputation was performed in 27 diabetic patients and debridement after minor amputation in three. The non-diabetic patients were scheduled for orthopaedic foot or ankle surgery. Conversion to general anaesthesia was not required in any patient. Supplementation of anaesthesia because of incomplete sensory blockade in the saphenous nerve territory, but not in the sciatic nerve territory, was necessary in one non-diabetic patient and in three diabetic patients.
All non-diabetic patients exhibited a visible motor response during stimulation with a current intensity of 1 mA without direct needle-nerve contact. The distance between needle tip and epineurium was 0.18 (0.14 to 0.21) cm. A motor response during stimulation with a current intensity of 1 mA, without direct needle–nerve contact, could not be obtained in diabetic patients. The electrical stimulation threshold, assessed when the needle tip was positioned directly adjacent to the peroneal component of the sciatic nerve, is presented in Fig. 1. Analysis of the loge-transformed data revealed a geometric mean of 0.26 (95% CI 0.24 to 0.28) mA in non-diabetic patients. In diabetic patients, the geometric mean was 1.9 (95% CI 1.6 to 2.2) mA. The geometric mean of the electrical stimulation threshold was significantly (P < 0.001) increased by a factor of 7.2 (95% CI 6.1 to 8.4) in diabetic compared to non-diabetic patients. Details of the electrical nerve stimulation threshold in diabetic and non-diabetic patients are provided in the supplemental Table 1, http://links.lww.com/EJA/A35.
Our study revealed a seven-fold increase in the electrical stimulation threshold of the sciatic nerve in patients with diabetic foot gangrene, compared to a patient cohort without diabetes mellitus. In contrast to non-diabetic patients, we observed large variability of the minimum current required to elicit a motor response in diabetic patients.
Electrical stimulation threshold in diabetic patients
There is a considerable prevalence of peripheral neuropathy in patients with type 1 or 2 diabetes mellitus.21,22 Motor and sensory peripheral nerve function deteriorates in tandem with the occurrence of microangiopathy23 and predicts the development of foot ulceration.24 Peripheral motor neuropathy may be associated with an increase in the electrical stimulation threshold of the nerve.25 Bigeleisen et al. 8 observed this phenomenon in seven diabetic patients when performing a supraclavicular brachial plexus block (median stimulation threshold 1.3 mA in diabetic patients vs. 0.5 mA in non-diabetic patients). We found a higher stimulation threshold than Bigeleisen et al. in our diabetic patients,8 which may be indicative of differences in the severity of diabetic neuropathy in the patient cohorts. It is unknown whether the alteration of the electrical motor response threshold varies between the brachial plexus and the sciatic nerve in diabetic patients because of the specific pattern of nerve injury in diabetic neuropathy.26 Only a few case reports have been published that describe difficulties in identifying the sciatic nerve in diabetic patients by electrical nerve stimulation.10–12 Sites et al.9 reported on two patients with ultrasound-guided popliteal fossa blocks who required a minimum current of 2.4 and 2.6 mA, respectively, to elicit a motor response of the sciatic nerve. Other authors, however, performed sciatic nerve blocks in diabetic patients and were obviously successful in localising the nerve by electrical stimulation, although the stimulation threshold was not reported.27 Our data put these case reports in a systematic context. The minimum stimulating current required to elicit a motor response was increased in the diabetic patients, thus making correct localisation of the sciatic nerve in accordance with established recommendations on the required stimulation threshold (0.2 to 0.5 mA) difficult.20
Consequences for patients with diabetic foot gangrene
There is an ongoing discussion as to whether a peripheral nerve block is associated with a higher incidence of perioperative nerve damage in patients with diabetes mellitus compared to patients without diabetes mellitus.28,29 Our findings draw attention to another aspect which may contribute to nerve damage during regional anaesthesia in patients with diabetes mellitus, namely difficulties with correct needle placement. Animal studies demonstrated that the intrafascicular (i.e. subperineural) injection of local anaesthetics is associated with nerve damage.30 Rigaud et al. 31 observed in non-diabetic dogs that a motor response of the sciatic nerve was achieved at low currents [0.33 (0.08) mA] when the needle was placed epineurally. In chemically induced (alloxan or streptozotocin) diabetic dogs, however, the needle had to be placed intraneurally to achieve a motor response. Although acute drug-induced metabolic changes are not comparable to the effects of long-lasting diabetes mellitus, an editorial comment emphasised the need for further research on nerve stimulation in patients with diabetes mellitus.32 As the stimulation threshold is markedly lower when the needle is placed intraneurally compared to extraneurally (in non-diabetic, as well as in diabetic patients),8 efforts to identify nerves by electrical stimulation in patients with the severe long-term complications of diabetes mellitus may be associated with an increased risk of intraneural needle placement.
Electrical stimulation threshold in non-diabetic patients
The current intensity required to elicit a motor response was consistently low in our non-diabetic patients and, thus, comparable to that reported by other authors.18,19 We noticed the spread of fluid around the nerve and the absence of compartmentalisation when injecting local anaesthetics, both indicating the avoidance of subperineural injection in our patients.33 Nevertheless, it could be questioned whether the ultrasound control of the needle tip position is able detect a partial penetration of the epineural sheath, which might influence the motor response threshold to electrical stimulation.
The definition of our diabetic patient cohort was clinically based. We included patients undergoing surgery due to diabetic foot gangrene. These patients typically present with sensory and motor polyneuropathy, which has been described as a multifactorial process caused by hyperglycaemia, inflammation and lipid metabolism.34 Additional factors may contribute to neuropathy in diabetic patients, such as renal disease or chronic inflammatory processes.35 Furthermore, neuropathy is associated with muscular atrophy,36 which might further alter the motor response to nerve stimulation.
There were significant differences between patient groups with respect to age, sex, comorbidities and long-term medication. Mechanisms such as the degeneration of axons and alterations in the myelin sheaths occur in aging patients.37 The amplitude of the compound muscle action potentials of the tibial nerve decrease markedly with age.38 Inflammatory cascades, which may have been induced in our patients with diabetic gangrene, additionally contribute to the damage of nerve axons.39 We are not aware that the medication of our patients could have contributed to neuropathy.40 Sex differences have been reported in patients with diabetic foot syndrome, as this disease more commonly affects male patients suffering from motor neuropathy than female patients.41 A recent study has also demonstrated that in female patients intrathecal bupivacaine had a great potency than that seen in male patients.42 It is unknown whether there are also differences between men and women in the electrical stimulation threshold of nerves, especially when these patients suffer from diabetes mellitus. Such a phenomenon might have contributed in addition to the huge difference in the electrical stimulation threshold between our diabetic and non-diabetic patients, which is much more pronounced than that observed in a previous study.8 This issue should be subject of further research, as well as the question as to whether the electrical nerve stimulation threshold is increased in diabetic patients without clinical signs of long-term complications. We did not assess further details of diabetic neuropathy, such as the grade of sensory disturbance, signs of autonomic neuropathy and impairment of nerve conduction, as a systematic examination was impossible owing to the clinical condition of many of the patients. Sciatic nerve blockade was performed approximately 10 cm proximal to the popliteal fossa crease, independently of the exact location of the sciatic nerve bifurcation. Previous studies found that the division of the sciatic nerve was located between 0 and 11.5 cm proximal to the popliteal crease.43 Despite performing the block proximal to the obvious division of the nerve, the separation of the sciatic nerve into two adjacent components was occasionally visible. It is unknown whether this phenomenon has an impact on the electrical stimulation threshold.
In conclusion, we found that the minimum current required to elicit a motor response of the sciatic nerve was substantially increased in patients with diabetic foot gangrene, with considerable variability. The geometric mean of the electrical stimulation threshold was increased by a factor of 7.2 (95% CI 6.1 to 8.4) in diabetic patients compared to non-diabetic patients. This phenomenon might complicate the identification of the sciatic nerve by electrical nerve stimulation in this patient cohort.
Assistance with the article: none declared.
Financial support and sponsorship: none declared.
Conflicts of interest: none declared.
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