Orthopedics

Feature Article 

Cuff Width Increases the Serum Biochemical Markers of Tourniquet-induced Skeletal Muscle Ischemia in Rabbits

Byron E. Chalidis, MD; Efstathios Kalivas, MD; Marina Parziali, MD; Anastasios G. Christodoulou, MD; Christos G. Dimitriou, MD

Abstract

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.

Drs Chalidis, Kalivas, Parziali, Christodoulou, and Dimitriou are from the First Orthopaedic Department, Aristotle University of Thessaloniki, “G. Papanikolaou” Hospital, Thessaloniki, Greece.

Drs Chalidis, Kalivas, Parziali, Christodoulou, and Dimitriou have no relevant financial relationships to disclose.

Correspondence should be addressed to: Byron E. Chalidis, MD, First Orthopaedic Department, Aristotle University of Thessaloniki, “G. Papanikolaou” Hospital, Exohi, 57010, Thessaloniki, Greece (byronchalidis@gmail.com).

Abstract

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.

Drs Chalidis, Kalivas, Parziali, Christodoulou, and Dimitriou are from the First Orthopaedic Department, Aristotle University of Thessaloniki, “G. Papanikolaou” Hospital, Thessaloniki, Greece.

Drs Chalidis, Kalivas, Parziali, Christodoulou, and Dimitriou have no relevant financial relationships to disclose.

Correspondence should be addressed to: Byron E. Chalidis, MD, First Orthopaedic Department, Aristotle University of Thessaloniki, “G. Papanikolaou” Hospital, Exohi, 57010, Thessaloniki, Greece (byronchalidis@gmail.com).

Pneumatic tourniquet use in upper- and lower-extremity surgery is a common practice that aims to facilitate a bloodless surgical field. However, prolonged application of the inflated cuff may cause significant biochemical and ultrastructural changes in skeletal muscles and nerves due to subsequent limb ischemia.1 As a result, deep venous thrombosis, pulmonary and peripheral embolism, fall of arterial pressure, and neuromuscular lesions may be encountered.2–6

In an attempt to decrease the incidence of such complications, reduction in inflation time and cuff pressure and frequent intervening reoxygenation intervals during long surgical procedures have been suggested.7–10 Cuff width may also influence the soft tissue response according to contact area and to the longitudinal and transversal distribution of pressures.11–14 However, the effect of cuff width on skeletal muscle ischemia-reperfusion injury has not been clearly evaluated. The hypothesis of the current study was that wide cuffs produced the same serum metabolic changes as observed with narrow cuffs.

Materials and Methods

Animals and Experimental Design

The experimental protocol was approved by the Institutional Animal Care and Use Committee of “G. Papanikolaou” Hospital. All animals received humane care.15

Thirty-six New Zealand White rabbits weighing between 2.5 and 3.5 kg and aged between 6 and 12 months were anesthetised via subcutaneous injection of ketamine (50 mg/kg) and fentanyl (0.2 mg/kg) prior to tourniquet application. They were placed in the supine position (Figure 1). A 2- or 4-cm-wide curved tourniquet cuff was wrapped around the mid-portion of the thigh (right hindlimb) and secured with circumferential tape to prevent distal displacement. Both cuffs had the same 19-cm length as recommended by Pedowitz.6 After gravity exsanguination, the tourniquet was inflated to either 200 or 400 mm Hg.

Photograph of the experimental setup. A 2- or 4-cm tourniquet cuff was applied to the rabbit’s back right hindlimb and inflated to a 200 or 400 mm Hg pressure.

Figure 1: Photograph of the experimental setup. A 2- or 4-cm tourniquet cuff was applied to the rabbit’s back right hindlimb and inflated to a 200 or 400 mm Hg pressure.

Combining 2 levels of tourniquet width (2 or 4 cm) and cuff pressure (200 or 400 mm Hg) produced 4 groups of 9 animals each: group A=2-cm cuff and 200 mm Hg pressure; group B=2-cm cuff and 400 mm Hg pressure; group C=4-cm cuff and 200 mm Hg pressure; group D=4-cm cuff and 400 mm Hg pressure. The method of randomization was a 1-to-1 allocation.

The tourniquet was applied for 2 hours. Blood samples were taken from the ipsilateral femoral vein, proximally to cuff location, before tourniquet inflation and 1, 5, and 30 minutes after cuff release. The serum levels of potassium,16–18 lactic acid,17–20 urea,17,19,20 serum creatinine phosphokinase MM isoenzyme (CPK-MM),18,21–25 and serum lactic dehydrogenase18,21–25 were measured as indicators of local limb ischemia. The rabbits were euthantized with a barbiturate overdose (100 mg/kg of pentobarbital intravenously).

Statistical Analysis

Statistical evaluation was performed with SPSS version 17 software package (SPSS Inc, Chicago, Illinois). Matched pair t test was used to detect changes in biochemical parameters. Data were subjected to 1-way analysis of variance and pairwise multiple comparison procedures (Holm-Sidak method) to look for differences among the 4 groups. P<.05 was considered significant.

Results

In all groups, blood serum potassium concentration increased in the first minute following cuff release (P<.001) but returned to normal levels after 30 minutes (P>.12). Potassium values did not differ among the 4 groups (Figure 2A).

Line graphs representing the change of mean values of the examined biochemical markers during experiment. At each time point, the F and P values are presented. The asterisk indicates statistical significance. Potassium (K): No differences were identified among the 4 groups at all time points (A). Lactic acid: One-way analysis of variance (ANOVA) revealed significant differences among groups. Holm-Sidak test revealed differences between groups A and B (P<.001), A and D (P<.001), B and C (P<.001), and C and D (P<.001) at all time points (B). Urea: One-way ANOVA revealed significant differences among groups. Holm-Sidak test revealed differences between groups A and B (P<.001), A and D (P<.001), B and C (P<.001), and C and D (P<.001) at all time points (C). Lactic dehydrogenase (LDH): One-way ANOVA revealed significant differences among groups. Holm-Sidak test revealed differences between groups A and B (P<.001), A and C (P<.001 at 1 and 5 min; P<.022 at 30 min), A and D (P<.001), B and C (P<.001), and C and D (P<.001) at all time points. Significant differences also existed between groups B and D after 30 min (P<.001) (D). Creatinine phosphokinase MM isoenzyme (CPK-MM): One-way ANOVA revealed significant differences at all times after deflation of the cuff. Holm-Sidak test revealed differences between groups A and B (P<.001), A and D (P<.001), B and C (P<.001), and C and D (P<.001) at all time points. Significant differences also existed between groups B and D at 30 min (P<.001) (E).

Figure 2: Line graphs representing the change of mean values of the examined biochemical markers during experiment. At each time point, the F and P values are presented. The asterisk indicates statistical significance. Potassium (K): No differences were identified among the 4 groups at all time points (A). Lactic acid: One-way analysis of variance (ANOVA) revealed significant differences among groups. Holm-Sidak test revealed differences between groups A and B (P<.001), A and D (P<.001), B and C (P<.001), and C and D (P<.001) at all time points (B). Urea: One-way ANOVA revealed significant differences among groups. Holm-Sidak test revealed differences between groups A and B (P<.001), A and D (P<.001), B and C (P<.001), and C and D (P<.001) at all time points (C). Lactic dehydrogenase (LDH): One-way ANOVA revealed significant differences among groups. Holm-Sidak test revealed differences between groups A and B (P<.001), A and C (P<.001 at 1 and 5 min; P<.022 at 30 min), A and D (P<.001), B and C (P<.001), and C and D (P<.001) at all time points. Significant differences also existed between groups B and D after 30 min (P<.001) (D). Creatinine phosphokinase MM isoenzyme (CPK-MM): One-way ANOVA revealed significant differences at all times after deflation of the cuff. Holm-Sidak test revealed differences between groups A and B (P<.001), A and D (P<.001), B and C (P<.001), and C and D (P<.001) at all time points. Significant differences also existed between groups B and D at 30 min (P<.001) (E).

Lactic acid levels significantly increased in all groups throughout the 30-minute period (P<.001). Peak values were observed within 1 minute after cuff release. Lactic acid concentration was always significantly higher in the 400 mm Hg groups (B and D) compared with the 200 mm Hg groups (A and C) (P<.001). However, cuff width did not affect the levels because no significant difference was found between groups A and C (P>.22) and groups B and D (P>.16) (Figure 2B).

A continuing increase in urea concentration was observed (P<.001). Groups B and D had higher values than did groups A and C at all times (P<.001). However, between groups of the same inflation pressure (group A vs C and group B vs D), no significant difference was identified (P>.17 for both) (Figure 2C).

The concentration of lactic dehydrogenase progressively increased in all groups (P<.001). The values were significantly higher in the 400 mm Hg groups (B and D) compared with the 200 mm Hg groups (A and C) (P<.001). Subgroup analysis revealed that lactic dehydrogenase concentration was higher in group D compared with group B after 30 minutes (P<.001) but not earlier. Between groups A and C, lactic dehydrogenase levels were higher in group C at all time points (P<.02) (Figure 2D).

Creatinine phosphokinase MM isoenzyme values were continuously elevated in all groups (P<.001). Groups B and D showed higher values compared with groups A and C (P<.001). Compared with group B, group D had significantly higher CPK-MM concentration after 30 minutes (P<.001) but not earlier. Between groups A and C, no difference was found (P>.9) (Figure 2E; Table).

Mean Concentration of Serum Biochemical Markers Before and After Cuff Deflationa

Table: Mean Concentration of Serum Biochemical Markers Before and After Cuff Deflation

Discussion

Serum levels of lactic dehydrogenase and CPK-MMA were significantly greater when using wide cuffs with a high inflation pressure (400 mm Hg). Under a lower pressure (200 mm Hg), only lactic dehydrogenase values were significantly higher with wide cuffs compared with narrow ones. Kokki et al24 conducted a prospective, open-randomized study in 26 patients to determine whether the use of a low-pressure tourniquet system with a wide, curved cuff connected to a microprocessor pump was safer than a standard tourniquet system with a narrow, straight cuff using higher inflation pressures. No differences existed among the study groups, and no advantage of using a low-pressure tourniquet system with a wide-curved cuff over a high-pressure tourniquet system with a narrow-straight cuff was identified. This finding appears to be inconsistent with the authors’ observation that wide cuffs cause more muscle damage compared with narrow ones at high and low pressures.

Pressure delivery is greatly influenced by tourniquet size and the level of inflation pressure.26,27 Wide cuffs could induce a more physiologic and evenly distributed pressure.27 Furthermore, the pressure gradients in soft tissues are smaller and subsequently limit skeletal muscle necrosis or nerve dysfunction.26 Wide cuffs stop blood flow without complete collapse of the arteries, possibly due to the frictional resistance of the fluid flow along the compressed length.11–14 However, the current results failed to confirm these findings because wide cuffs caused significantly more skeletal damage compared with narrow ones.

According to the current study, high inflation pressures strongly affect skeletal muscle damage, particularly when combined with wide cuffs. Previous studies have shown that transmission of external cuff pressure to soft tissues and minimum arterial occlusion threshold may change according to the tourniquet’s width.11–14,28,29 Graham et al30 reported the Doppler occlusion pressure in the upper and lower extremities of 34 normotensive volunteers. A constant inverse relationship existed between occlusion pressure and the ratio of cuff width to limb circumference.30 Crenshaw et al31 reported that wide cuffs were associated with a greater variety of applied pressure values as a result of the larger contact area. Broad cuffs transmitted more pressure to deep tissues compared with conventional cuffs, and, therefore, lower pressures were required to interrupt limb circulation.31 Pedowitz et al10 reported more focal fiber necrosis and local cellular infiltration in rabbits’ thigh muscles following tourniquet application with 350 mm Hg rather than 125 mm Hg cuff pressures. Using the same animal model, Nitz et al5 reported that cuff pressure level was the main factor responsible for nerve injury.

Regarding the clinical effect of cuff width, wider cuffs may be more easily tolerated by obese patients because they could achieve blood occlusion at lower pressures.32 Estebe et al33 reported that a wide tourniquet cuff is less painful than a narrow cuff if inflated at lower pressures and that at these lower pressures it is still effective at occluding blood flow. Newman and Muirhead11 reported that broad cuffs combined with lower pressures performed well in terms of patient satisfaction and complication rates postoperatively. Specifically, a 12.5-cm pneumatic tourniquet inflated to a relatively low pressure was found to provide the same level of satisfaction but fewer postoperative distal paresthesias compared with a 9-cm tourniquet inflated to an arbitrary but significantly higher pressure.11 In addition, Mittal et al34 investigated the effect of different width cuffs on the motor nerve conduction of the median nerve and reported that wider cuffs resulted in more severe changes in nerve conduction velocity than narrow ones. Although a wide cuff submits a greater mass of tissue to compression, its effectiveness at lower inflation pressures may reduce the risk of nerve injury.11

The current study’s methodology was in accordance with previous studies that used the same blood biochemical markers to evaluate the level of skeletal muscle ischemia-reperfusion injury.16,18,19,24,25,35 However, the study had 2 limitations. No subcutaneous, muscular, or nerve tissue samples under the tourniquet were received for histologic examination. Therefore, the specific effect of cuff breadth on muscle function, metabolism, and nerve conduction was not explored. Second, the same cuff pressures were applied in both tourniquet types. Because wide tourniquet cuffs have been advocated to be equally effective and safer at low pressures, the values of biochemical-examined parameters may be different if the selected inflation pressures were adjusted according to the minimum arterial occlusion threshold value.

Conclusion

Serum biochemical markers of inducible skeletal muscle ischemia-reperfusion injury were increased using a wide cuff with a high inflation pressure. Under the same inflation pressure, broad tourniquets caused greater skeletal muscle damage compared with narrow ones.

References

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Mean Concentration of Serum Biochemical Markers Before and After Cuff Deflationa

After
Marker Before 1 min 5 min 30 min
Potassium, mEq/L
  Group A 3.50 6.29b 4.06b 3.70c
  Group B 3.89 6.38b 4.07d 3.90c
  Group C 3.60 5.89b 3.80d 3.40c
  Group D 3.70 6.07b 4.30b 3.82c
Lactic acid, mg/dL
  Group A 49.00 64.22b 60.67b 57.33b
  Group B 45.89 78.00b 69.00b 66.67b
  Group C 46.78 66.00b 59.00b 56.00b
  Group D 48.11 77.67b 70.78b 68.67b
Urea, mg/dL
  Group A 33.56 44.00b 47.00b 49.00b
  Group B 32.67 52.00 b 56.00b 59.00b
  Group C 31.44 42.00b 48.00b 50.00b
  Group D 32.67 51.00b 54.00b 58.00b
LDH, IU/L
  Group A 98.78 323.44b 377.00b 380.00b
  Group B 97.89 452.67b 484.89b 509.00b
  Group C 90.11 368.44b 394.00b 406.33b
  Group D 100.67 448.78b 476.78b 554.56b
CPK-MM, IU/L
  Group A 148.22 299.22b 312.78b 598.00b
  Group B 142.11 349.67b 396.33b 723.00b
  Group C 149.89 304.89b 319.78b 593.00b
  Group D 143.56 361.00b 412.33b 838.89b

10.3928/01477447-20120725-27

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