Carpal tunnel release under wide awake local anesthesia with no tourniquet in hemodialysis patients with arteriovenous shunt.

INTRODUCTION: Long-term hemodialysis patients experience many hand diseases caused by dialysis-related amyloidosis (DRA), with carpal tunnel syndrome (CTS) being the most common. For the patients with arteriovenous (AV) shunt, surgical decompression remains challenging because of the contraindications of a tourniquet. A technique called wide-awake local anesthesia with no tourniquet (WALANT), in which epinephrine provides hemostasis instead of the tourniquet, can be a good option for hemodialysis patients. The purpose of this study was to assess the prevalence of CTS and related factors in hemodialysis patients, and to establish the efficacy and safety of WALANT on hemodialysis patients with AV shunt. MATERIALS AND METHODS: This prospective study included 275 hemodialysis patients between March 2013 and July 2019. 43 patients were diagnosed with CTS, involving surgical treatment on 70 wrists. We performed mini-open carpal tunnel release using WALANT on the AV shunt arm (defined as the WALANT group), while using lidocaine and a tourniquet on the arm without an AV shunt (defined as the tourniquet group). The operative time, surgical field bleeding (blood loss and hemostasis score), surgical pain (injection pain and tourniquet pain), outcomes, complications, and satisfaction were compared between the two groups. RESULTS: The incidence of CTS in hemodialysis patients was 15.6%. Longer dialysis durations were related to higher proportions of patients with CTS. There was no significant difference in blood loss (p=0.184) and hemostasis score (p=0.165) between the two groups. Clinical symptoms improved in all patients, and there were no severe complications. The WALANT group had a significantly longer preparation time of approximately 20minutes, but they had low injection pain and no tourniquet pain. There was also no significant difference in terms of satisfaction levels (p=0.212). DISCUSSION: CTS is a very common disease among hemodialysis patients. WALANT provided sufficient hemostasis without a tourniquet, despite the patients' high bleeding tendency. The technique also had the advantages of low injection pain, no tourniquet pain, and no major complications. In this respect, WALANT can be a good choice for hemodialysis patients with AV shunt. LEVEL OF EVIDENCE: II.

Patients' Perspective on Carpal Tunnel Release with WALANT or Intravenous Regional Anesthesia.

BACKGROUND: The authors conducted a prospective study to compare patients' intraoperative experience of open carpal tunnel release under "wide awake, local anesthesia, no tourniquet" (WALANT) on the one hand and intravenous regional anesthesia on the other. The authors hypothesized that WALANT would offer a better intraoperative experience than intravenous regional anesthesia. METHODS: Twenty-four patients with bilateral carpal tunnel syndrome had one hand operated on using WALANT and the contralateral hand with the intravenous regional anesthesia method. At the postoperative second hour, patients completed a questionnaire to quantify their pain levels on a numerical rating scale and compare the operation with dental procedures. They were also asked about their expectations and feelings about reoperation with the anesthesia methods. The results were compared for the two anesthesia methods. RESULTS: There were no significant differences between numerical rating scale pain values during anesthetic administration or for surgical site pain on the WALANT and intravenous regional anesthesia sides. Patients reported moderate tourniquet pain for intravenous regional anesthesia sides. For WALANT sides, a significantly higher number of patients reported carpal tunnel release to be an easier procedure than dental procedures (91.6 percent WALANT and 37.5 percent intravenous regional anesthesia). For WALANT sides, a significantly higher number of patients reported carpal tunnel release to be an easier procedure than they expected (91.6 percent WALANT and 50 percent intravenous regional anesthesia). For the reoperation, 83.3 percent of patients preferred WALANT, 8.3 percent preferred intravenous regional anesthesia, and 8.3 percent reported no preference. CONCLUSIONS: WALANT offered a better intraoperative experience. Tourniquet pain, preoperative preparation basics, and the extended anesthesia duration are likely the major drawbacks of the intravenous regional anesthesia method.

The Possible Pathophysiological Outcomes and Mechanisms of Tourniquet-Induced Ischemia-Reperfusion Injury during Total Knee Arthroplasty.

Ischemia and reperfusion (I/R) injury induced by tourniquet (TQ) application leads to the release of both oxygen free radicals and inflammatory cytokines. The skeletal muscle I/R may contribute to local skeletal muscle and remote organ damage affecting outcomes after total knee arthroplasty (TKA). The aim of the study is to summarize the current findings associated with I/R injury following TKA using a thigh TQ, which include cellular alterations and protective therapeutic interventions. The PubMed database was searched using the keywords "ischemia reperfusion injury," "oxidative stress," "tourniquet," and "knee arthroplasty." The search was limited to research articles published in the English language. Twenty-eight clinical studies were included in this qualitative review. Skeletal muscle I/R reduces protein synthesis, increases protein degradation, and upregulates genes in cell stress pathways. The I/R of the lower extremity elevates local and systemic oxidative stress as well as inflammatory reactions and impairs renal function. Propofol reduces oxidative injury in this I/R model. Ischemic preconditioning (IPC) and vitamin C may prevent oxygen free radical production. However, a high dose of N-acetylcysteine possibly induces kidney injury. In summary, TQ-related I/R during TKA leads to muscle protein metabolism alteration, endothelial dysfunction, oxidative stress, inflammatory response, and renal function disturbance. Propofol, IPC, and vitamin C show protective effects on oxidative and inflammatory markers. However, a relationship between biochemical parameters and postoperative clinical outcomes has not been validated.

Effect of two administration routes of Shenmai Injection () on pulmonary gas exchange function after tourniquet-induced ischemia-reperfusion.

OBJECTIVE: To compare the effect between nebulized and intravenous administration of Shenmai Injection () on pulmonary gas exchange function of patients following tourniquet-induced lower limb ischemia-reperfusion. METHODS: Thirty-eight patients scheduled for lower extremity surgery were randomized into three groups using the closed envelop method: Shenmai Injection was administered 30 min before tourniquet inflflation by nebulization [0.6 mL/kg in 10 mL normal saline (NS)] in the nebulization group or by intravenous drip (0.6 mL/kg dissolved in 250 mL of 10% glucose) in the intravenous drip group, and equal volume of NS was given intravenously in the NS group; 15 in each group. Arterial blood gases were analyzed, serum levels of malonaldehyde (MDA) and interleukine-6 (IL-6) and interleukine-8 (IL-8) were determined using the method of thiobarbituric acid reaction and enzyme-linked immuno sorbent assay respectively just before tourniquet inflflation (T0), and at 0.5 h (T1), 2 h (T2), 6 h (T3) after tourniquet deflflation. RESULTS: Compared with baselines at T0, MDA levels signifificantly increased at T2, T3 in the NS group and at T3 in the nebulization group, and IL-6 and IL-8 levels were signifificantly increased at T2, T3 in NS, the intravenous drip and the nebulization groups (P <0.05). Arterial pressure of oxygen (PaO2) at T3 was decreased, while alveolararterial oxygen tension showed difference (PA-aDO2) at T3 in the NS group; RI at T3 in both intravenous drip and the nebulization groups were enhanced (P <0.05). Compared with the NS group, MDA and IL-8 levels at T2, T3, IL-6 at T3 in the intravenous drip group, and IL-8 at T3 in the nebulization group were all remarkably increased (P <0.05). Additionally, MDA level at T3 in the nebulization group was higher than that in the intravenous drip group (P <0.05). CONCLUSIONS: Intravenous administration of Shenmai Injection provided a better protective effect than nebulization in mitigating pulmonary gas exchange dysfunction in patients following tourniquet-induced limb ischemia-reperfusion.

Effects of topical combinations of clonidine and pentoxifylline on capsaicin-induced allodynia and postcapsaicin tourniquet-induced pain in healthy volunteers: a double-blind, randomized, controlled study.

This double-blind randomized controlled study was designed to evaluate the analgesic effects of topical treatments with clonidine (CLON) and pentoxifylline (PTX) tested alone or as low- and high-dose combinations in a human experimental model of pain. Of 69 healthy subjects aged 18 to 60 years, 23 each were randomly allocated to low-dose (0.04% + 2%) and high-dose (0.1% + 5%) CLON + PTX groups. Both of these groups also received their corresponding placebos in one of 2 treatment periods separated by at least 48 hours. Twenty-three additional subjects received either CLON (0.1%) or PTX (5%) as single drug treatments, in each of 2 treatment periods. Assessment of analgesic efficacy was based on allodynic effects of previous intraepidermal capsaicin injection, as well as postcapsaicin tourniquet-induced pain 50 minutes following capsaicin injection. Visual Analogue Scale (VAS) ratings of pain intensity and the area of dynamic mechanical allodynia were the primary outcome measures, whereas area of punctate mechanical allodynia (PMA) served as a secondary outcome measure. Topical treatments with high- or low-dose combinations significantly reduced VAS ratings compared with corresponding placebo treatments throughout the period of postcapsaicin tourniquet-induced pain. Importantly, the high-dose combination produced lower VAS ratings than CLON alone, which were lower than PTX alone. Results also revealed significant inhibition of postcapsaicin dynamic mechanical allodynia and PMA for the high-dose combination compared with placebo, and of PMA for CLON compared with the low-dose combination. Hence, the present data are supportive of further clinical investigation of the high-dose topical combination of CLON + PTX in complex regional pain syndrome and neuropathic pain patients, for which our preclinical data predict efficacy.

Cuff width increases the serum biochemical markers of tourniquet-induced skeletal muscle ischemia in rabbits.

Tourniquet application is a widely accepted adjuvant technique in extremity surgery. The purpose of this prospective, randomized trial was to evaluate the effect of cuff width on skeletal muscle ischemia-reperfusion injury. A 2- or 4-cm wide curved tourniquet cuff was applied around the midthigh of 36 New Zealand White rabbits and inflated to a pressure of 200 or 400 mm Hg for 2 hours: group A=2 cm to 200 mm Hg; group B=2 cm to 400 mm Hg; group C=4 cm to 200 mm Hg; group D=4 cm to 400 mm Hg. Blood levels of potassium, lactic acid, urea, lactic dehydrogenase, and creatinine phosphokinase MM isoenzyme (CPK-MM) were measured as basic indicators for limb ischemia before tourniquet inflation and 1, 5, and 30 minutes after cuff release.Potassium values did not differ among the 4 groups. Lactic acid and urea concentrations were always higher in the 400 mm Hg groups (B and D) (P<.001). However, cuff width did not affect their levels (P>.16). Lactic dehydrogenase and CPK-MM values were also greater in the 400 mm Hg groups at all times (P<.001). Further subgroup analysis of 200 mm Hg pressure groups showed higher lactic dehydrogenase (P<.02) but not CPK-MM (P>.9) concentrations in group C than in group A during the 30-minute period. At 400 mm Hg, lactic dehydrogenase and CPK-MM values were higher in group D compared with group B only 30 minutes after cuff deflation (P<.001). Broad tourniquets are associated with significantly greater and prolonged elevation of serum biochemical markers of inducible skeletal muscle ischemia-reperfusion injury compared with narrow ones. This difference is more prominent when a wide cuff is inflated to a high pressure.

Comparison of pain perceived when using pneumatic or silicone ring tourniquets for local anaesthetic procedures in the upper limb.

The aim of this study was to evaluate the level of pain felt when silicone ring and pneumatic tourniquets were applied to the upper arm and to determine which was more suitable for use in local anaesthetic procedures. Pain was measured using a visual analogue score pain scale on application and at 1, 5, and 10 minutes in 30 volunteers. Volunteers experienced significantly more pain on application and at 1 and 5 minutes with the silicone ring tourniquet. This difference in pain was most marked on application. Two volunteers could not tolerate application of the silicone ring tourniquet. We conclude that the silicone ring tourniquet would not be suitable for local anaesthetic procedures in the upper limb due to the severe pain experienced on application, which may reduce the patients' confidence and adversely affect their experience of the procedure. The pneumatic tourniquet is more suitable for local procedures.

[Role of vascular endothelial active facters in gas exchange impairment induced by tourniquet and the effect of shenmai injection].

OBJECTIVE: To investigate the effect of Shenmai injection on vascular endothelial active facters nitric oxide (NO) and endothelin-1 (ET-1), and pulmonary gas exchange induced by tourniquet deflation in patients undergoing lower extremity surgery. METHOD: Twenty-six patients scheduled for unilateral lower extremity surgery were randomly divided into 2 groups: control group (group C, n = 14) and Shenmai injection group (group SM, n = 12). All the patients agreed to a combined spinal-epidural anesthesia at the L2-L3 interspace and a radial artery catheter was placed for sampling. Patients in group SM were injected Shenmai injection 0.6 mL x kg(-1) and physiological saline 100 mL, while patients in group C were injected equal volume of normal saline instead 15 min before tourniquet inflation. Blood samples which were used for blood gas analysis and measurement of nitric oxide (NO) and endothelin-1 (ET-1) were taken before tourniquet inflation (T0, baseline) and 30 min (T1), 2 h (T2), 6 h (T3), 24 h (T4) after tourniquet deflation. RESULT: Compared with the baseline values at T0, in group C at T3 P(a) O2 and the levels of NO were significantly decreased, while P(A-a) DO2 and the levels of ET-1 at T3 were significantly increased (P < 0.05 or P < 0.01), in group SM, the levels of NO at T3 were significantly decreased (P < 0.05). Compared with group C, the changes of P(a)O2, P(A-a) DO2, NO and ET-1 were significantly mitigated in group SM. CONCLUSION: The concentrations of NO and ET-1 is connected with the pulmonary gas exchange impairment induced by tourniquet application. Shenmai injection can improve the pulmonary gas exchange based on rising the level of NO, reducing the level of ET-1.

Effect of Shenmai injection, a traditional Chinese medicine, on pulmonary dysfunction after tourniquet-induced limb ischemia-reperfusion.

BACKGROUND: Tourniquet has been considered as a recognized cause of lower limb ischemia-reperfusion injury in the orthopedic field. This study investigates pulmonary function after tourniquet deflation and the protective effect of Shenmai injection (SMI), a traditional Chinese medicine. METHODS: Twenty-eight patients undergoing lower extremity surgery were randomized into a control group (group C) and a SMI group (group S), 14 patients in each group. Blood gas and circulating indicators (malondialdehyde, interleukin [IL]-6, and IL-8) were measured immediately before tourniquet inflation and at 0.5 hour, 2 hours, 6 hours, and 24 hours after tourniquet deflation. RESULTS: Plasma levels of malondialdehyde, IL-6, and IL-8 in group C were significantly increased over baselines from 2 hours to 24 hours after tourniquet deflation and the levels reached their peaks at 6 hours after tourniquet deflation, when arterial partial pressures of oxygen and arterial-alveolar oxygen tension ratio were decreased, whereas alveolar-arterial oxygen difference was increased significantly. Both the changes in blood gas variables and plasma mediators were attenuated in group S. CONCLUSION: Pulmonary gas exchange is impaired after lower limb ischemia-reperfusion induced by clinical tourniquet application. Pretreatment with SMI, a traditional Chinese medicine, attenuates lipid peroxidation and systemic inflammatory response and mitigates pulmonary dysfunction.

Multiple digital gangrene arising from traditional therapy: a case report.

BACKGROUND: Traditional medicine has being advocated as an alternative to Orthodox medicine in Nigeria despite, its reported adverse effects. OBJECTIVE: To report an unusual complication of traditional therapy. METHODS: A 20-year-old house-wife who was bitten by a crawling insect presented to a hospital with complaints of swollen body and pain in three digits. After clinical evaluation and investigations, she had both medical and surgical intervention. RESULTS: Two weeks following an insect bite, the patient noticed periorbital and bilateral leg swellings. She sought help from a traditional medicine practitioner who incised and tied the affected digits for three days. He repeated the cycle thrice. She had generalized oedema, massive proteinuria, hypoalbuminaemia, hypercholesterolaemia features consistent with a diagnosis of nephritic syndrome. There was gangrene of the left middle finger and both index toes. Oedema responded to diuretics, lisinopril and low salt diet. She had surgery for the gangrenous digits. CONCLUSION: Development of gangrene is an unusual finding in nephrotic syndrome. It occurred in this case as an aftermath of traditional medical intervention. This report reiterates the danger of this form of medical practice and the need for measures to protect the populace to be put in place.

Multiple digital grengrene arising from traditional therapy: a case report.

BACKGROUND: Traditional medicine has being advocated as an alternative to Orthodox medicine in Nigeria despite, its reported adverse effects. OBJECTIVE: To report an unusual complication of traditional therapy. METHODS: A 20-year-old house-wife who was bitten by a crawling insect presented to a hospital with complaints of swollen body and pain in three digits. After clinical evaluation and investigations, she had both medical and surgical intervention. RESULTS: Two weeks following an insect bite, the patient noticed periorbital and bilateral leg swellings. She sought help from a traditional medicine practitioner who incised and tied the affected digits for three days. He repeated the cycle thrice. She had generalized oedema, massive proteinuria, hypoalbuminaemia, hypercholesterolaemia features consistent with a diagnosis of nephritic syndrome. There was gangrene of the left middle finger and both index toes. Oedema responded to diuretics, lisinopril and low salt diet. She had surgery for the gangrenous digits. CONCLUSION: Development of gangrene is an unusual finding in nephrotic syndrome. It occurred in this case as an aftermath of traditional medical intervention. This report reiterates the danger of this form of medical practice and the need for measures to protect the populace to be put in place.

Evaluation of the efficacy of magnesium sulphate as an adjuvant to lignocaine for intravenous regional anaesthesia for upper limb surgery.

Several additives have been combined with local anaesthetics for intravenous regional anaesthesia to improve block quality, analgesia and to decrease tourniquet pain. Magnesium sulphate is one potential additive. This prospective, randomised, double-blinded study was conducted in 30 ASA physical status I or II patients undergoing upper limb surgery under tourniquet. In group L, patients received intravenous regional anaesthesia with lignocaine alone (9 ml of 2% lignocaine diluted with normal saline to total volume of 36 ml). Patients in group M received intravenous regional anaesthesia with lignocaine plus magnesium sulphate (6 ml of 25% magnesium sulphate plus 9 ml of 2% lignocaine diluted with normal saline to total volume of 36 ml). Assessment was by observing the response to injection of drug; sensory and motor block and tourniquet pain. The mean time of onset of sensory block was 12.40 and 3.47 minutes in groups L and M respectively (P < 0.001). The average times of onset of motor block in groups L and M were 17 and six minutes respectively (P < 0.001). Of the patients in group M, 66.7% reported moderate to severe pain while the drug was being injected, compared to 20% in group L (P=0.011). There was a statistically significant difference in visual analogue scale for tourniquet pain at 10 and 30 minutes after tourniquet inflation (lower in group M). These findings indicate that magnesium sulphate added as an adjuvant to lignocaine hastens the onset of sensory and motor block and decreases tourniquet pain. However there is increased incidence of transient pain on injection if magnesium sulphate is added.

Carpal tunnel release using local anaesthetic and a forearm tourniquet.

Carpal tunnel release can be performed under general or local anaesthetic. However, many surgeons believe the upper arm tourniquet is not tolerated by the patient when awake. We use a forearm tourniquet for carpal tunnel decompression under local anaesthesia. The aim of this study is to assess patient tolerance of the technique. Between January 1st 1996 and December 31st 2000, 74 patients had carpal tunnel release performed using local anaesthesia. We sent a postal questionnaire to each, asking the patient to rate different aspects of the procedure. Fifty-eight patients replied (78% response). Forty-four of the respondents (76%) tolerated the tourniquet well, finding it to be 'no problem' or only 'mildly painful'. The same number reported they would prefer to have local anaesthesia again in the event of their requiring a similar operation on their hand. We believe carpal tunnel release using local anaesthetic and a forearm tourniquet is well tolerated by the patient.

Efficacy of forearm versus upper arm tourniquet for local anaesthetic surgery of the hand.

A prospective study was undertaken to compare the use of forearm and upper arm tourniquets for local anaesthetic procedures on the hand. One hundred consecutive patients with an upper arm tourniquet were compared with a further consecutive 100 patients in whom a forearm tourniquet was used. The tourniquet time was always less than 20 minutes and the scoring of perceived pain was not significantly different in the two groups. Use of a forearm tourniquet was well tolerated and was not associated with an increase in complications.

Traditional bone setter's gangrene.

Traditional bone setter's gangrene (TBSG) is the term we use to describe the sequelae sometimes seen after treatment with native fracture splints. Twenty five consecutive complications were recorded in 25 patients aged between 5-50 years with a median age of 10 years. The major complication of the native fracture splint treatment was distal limb gangrene necessitating proximal amputations in 15 cases.

Quantitative evaluation of tourniquet leak during i.v. regional anaesthesia of the upper and lower limbs in human volunteers.

Although it is accepted that during i.v. regional anaesthesia (IVRA) local anaesthetic can leak under the tourniquet into the systemic circulation, no published study has evaluated this leak quantitatively. In volunteers, during two random sessions, we have simulated IVRA using standard techniques with a radiolabelled compound which is chemically similar to lignocaine and has comparable tissue distribution (0.1 mg of HIDA labelled with 100 muCi of 99mTc in 40 ml of saline). The decrease in radioactivity was measured with a gamma camera for the 20 min of tourniquet inflation and for the 20 min of washout after cuff deflation. While the tourniquet was inflated, the leak for the lower limb (mean 29 (SD 8) %) was significantly greater (P < 0.004) than the leak for the upper limb (15 (5) %). Moreover, in each of 10 volunteers, the leak was always greater for the lower than the upper limb. During the first 3 min after tourniquet deflation the loss of radioactivity was 58 (8) % of the maximal amount for the upper limb and 39 (8) % for the lower limb (P < 0.001). As the leak under the tourniquet was significantly greater for the lower than the upper limb, we conclude that IVRA for the lower limb can be associated more frequently with a shorter duration of successful anaesthesia and/or failure.

Double-blind, placebo-controlled investigation of the effect of combined phototherapy/low intensity laser therapy upon experimental ischaemic pain in humans.

BACKGROUND AND OBJECTIVE: This study assessed the putative analgesic effect of combined monochromatic light/laser irradiation at low intensity (660-950 nm; 31.9 J/cm2; pulsed at 16 or 73 Hz). STUDY DESIGN/MATERIALS AND METHODS: The investigation was completed under double-blind conditions using a standardised form of the submaximal effort tourniquet technique. Healthy male volunteers naive to the experimental conditions (n = 45) attended on two occasions for the purposes of pain induction, the first during which baseline data were obtained and on a second occasion during which they were randomly allocated to one of two treatments or a placebo condition. For the treatment conditions, irradiation was applied to the ipsilateral Erb's point at the parameters stated; for the placebo condition, sham "irradiation" was delivered using a dummy unit. Pain was measured using computerised visual analogue scales and McGill Pain Questionnaires (MPQ) to assess "current pain intensity" and "worst pain experienced," respectively. RESULTS: Analysis of variance and appropriate post hoc tests demonstrated only a weak (but significant) hypoalgesic effect compared to placebo (P < 0.05) in the treatment group irradiated at 16Hz for the sensory component of the MPQ; other comparisons were found to be nonsignificant. CONCLUSIONS: These results do not provide convincing evidence for the hypoalgesic potential of combined monochromatic light/laser irradiation, at least at the parameters used here, and thus indicate the necessity of additional work to investigate this modality further in order to assess the potential benefit, if any, of such treatment in the clinical setting.

Effect of a eutectic mixture of local anaesthetic agents (EMLA) on tourniquet pain in volunteers.

We studied the effects of EMLA on tourniquet pain in 10 healthy male volunteers. The tourniquet inflation time which was tolerated was significantly longer with EMLA (46.4 (SEM 3.5) min) compared with placebo (37.5 (2.7) min) (P less than 0.05). Linear analogue pain scores increased in both groups over the study period, but were significantly less in the EMLA group at 40 min (P less than 0.05). We conclude that tourniquet pain has a significant cutaneous component.

[Effect of kontrikal on the dynamics of proteolytic system indices in postischemic toxemia]. / Vliianie kontrikala na dinamiku pokazatelei sistemy proteoliza pri postishemicheskoi toksemii.

It was shown in Wistar male rats that the development of tourniquet shock was followed by an increase of proteolytic activity in the blood by 3 times, activity of aspartate aminotransferase (AST) by 3 times, that of alanine aminotransferase (ALT) by 6 times, contents of urea and residual nitrogen by 2.5-3 times; level of alpha 1-protease inhibitor (alpha 1-PI) decreased by 4 times and that of alpha 2-macroglobulin (alpha 2MG) by 2.5 times. At administration of contrykal (10,000 U/kg) proteolytic activity increased only by 32.5%, content of alpha 1-PI decreased only by 10-20% and level of alpha 2-MG did not differ from that in healthy animals. Activity of AST and ALT remained high, and contents of urea and residual nitrogen were near-normal.

Optimizing tourniquet application and release times in extremity surgery. A biochemical and ultrastructural study.

Despite numerous studies investigating the pathophysiology of tourniquet ischemia, definitive data at the cellular level have been lacking and no consensus regarding safe tourniquet-application times in extremity surgery has emerged. In light of the particular vulnerability of skeletal muscle to ischemic injury, we determined the degree of muscular metabolic derangement and cell damage produced by seven different protocols of tourniquet application and release, each providing three hours of total tourniquet time. We performed thirty-six experiments on canine hind limbs, comparing the following time-patterns of tourniquet application: I--three sequential one-hour periods, II--two sequential one and one-half-hour periods, III--two hours followed by one hour, and IV--a single continuous three-hour application. Five and fifteen-minute reperfusion intervals between ischemic periods were compared for the first three time-patterns, creating a total of seven different tourniquet protocols. Muscular metabolic derangement and cell injury were evaluated by monitoring changes in the cellular bioenergetic state (high-energy phosphate profile), cell pH, post-ischemic leakage of creatine phosphokinase, and ultrastructural cell degeneration. At the intracellular level, the metabolic recovery of muscle during reperfusion was much faster than previous studies focusing on extracellular parameters have indicated. In all instances complete intracellular bioenergetic recovery occurred within five minutes after tourniquet release. The use of one or more five-minute reperfusion intervals significantly reduced the degree of ischemic cell injury, as indicated by a decrease in creatine phosphokinase leakage and myofibrillar destruction. No additional benefit was derived by extending the reperfusion periods to fifteen minutes. The longest period of continuous ischemia in each tourniquet-application protocol bore the closest relationship with the amount of cell damage produced. Within the spectrum of observed pathological changes, time-patterns I and II produced comparatively little muscle damage.