Using the Amplitude of Pulse-Synchronous Intramuscular Pressure Oscillations When Diagnosing Chronic Anterior Compartment Syndrome.

BACKGROUND: To diagnose chronic anterior compartment syndrome (CACS) among patients with exercise-induced leg pain, intramuscular pressure (IMP) is regarded as the gold standard. Two recent studies have suggested that the evidence for commonly used IMP criteria are weak, and the validity has therefore come under question.
PURPOSE: To evaluate whether the amplitude of pulse-synchronous IMP oscillations at rest after an exercise test is a reliable parameter that may aid in diagnosing CACS. STUDY
DESIGN: Cohort study (diagnosis); Level of evidence, 2.
METHODS: A total of 89 consecutive patients with suspected CACS (mean age, 31 years) and 19 healthy subjects (mean age, 28 years) participated in this study. All participants performed an exercise test until they were unable to continue because of leg pain and/or muscle fatigue. The IMP was recorded continuously in the anterior compartment of the leg with a noninfusion pressure recording system, starting 15 to 30 seconds after discontinuation of exercise. To test the amplitude of pulse-synchronous IMP oscillations as an indicator of CACS, a peak-to-peak amplitude of >2 mm Hg was chosen as the cutoff value. The clinical diagnosis of CACS was considered reference standard.
RESULTS: The mean ± SD IMP 1 minute after exercise was 54 ± 16 mm Hg in 53 patients with CACS, 17 ± 6 mm Hg in 36 non-CACS patients, and 18 ± 5 mm Hg in control subjects. The mean amplitude of the oscillations was 7.1 ± 3 mm Hg in patients with CACS, 1.3 ± 0.9 mm Hg in non-CACS patients, and 1.5 ± 0.6 mm Hg in control subjects 1 minute after exercise. The sensitivity of the amplitude to validate CACS was 96%, while the specificity was 94%. The positive predictive value was 96%, and the negative predictive value was 94%.
CONCLUSION: The amplitude of the pulse-synchronous IMP oscillations at rest after an exercise test that elicits a patient's leg pain and muscle fatigue has high sensitivity to identify an abnormally elevated IMP. CLINICAL RELEVANCE: Oscillations are easily recorded during clinical routine IMP measurements. They ascertain the diagnosis of CACS, corroborate the level of IMP, and ensure catheter patency.

In patients with exertional leg pain and suspected chronic compartment syndrome, the level of intramuscular pressure (IMP) is often regarded as the gold standard to support the patient's symptom history and clinical findings.[1,7,12] Recent systematic reviews report conflicting evidence regarding the validity of IMP level in diagnosing chronic compartment syndrome as well as an overlap in commonly used IMP criteria.[13,18] Another study concluded that the evidence for the commonly used IMP criteria is weak, but it found no overlap in reported mean IMP levels between patients and control subjects when IMP was measured 1 minute after exercise.[1] Since diagnosing chronic compartment syndrome based on patient history and clinical characteristics alone may lead to overdiagnosis,[2] improvements in using IMP as a parameter are needed.

A history of chronic anterior compartment syndrome (CACS) involves leg swelling, weakness of affected muscles, drop-foot symptoms, paresthesia, and pain (often throbbing) that forces the patient to discontinue exercising. The symptoms quickly abate after discontinuation of the inciting event. Postexercise clinical findings often include pain and tenderness at palpation, impaired muscle function, and a swollen compartment.

The volume of muscle tissue increases during exercise,[3,6] and the increase in volume reduces the compliance of the muscle compartment. Compliance is a measure of the elastic properties and is defined as volume change per unit of pressure change. Low compliance implies that a small change in muscle compartment volume produces a large change in IMP. Each arterial pulse in the affected compartment gives a pulse-synchronous transient volume increase in the muscle and oscillations of the IMP (Nilsson et al, unpublished data, 2014). Although a clinical study of patients with CACS observed that the arterial pulses are reflected by the IMP oscillations,[17] the diagnostic value of the amplitude of IMP oscillations is not known.

The purposes of this study were (1) to investigate the correlation between IMP at rest after an exercise test and the amplitude of the pulse-synchronous IMP oscillations in patients with or without CACS and in healthy control subjects and (2) to determine the sensitivity and specificity of the IMP amplitude oscillations in diagnosing CACS.

Materials and Methods

Subjects

A total of 89 consecutive patients (49 women, 40 men) with a mean age of 31 years (range, 16-69 years) with exercise-induced pain in the anterior part of the leg were included in the study. Most patients (60%) were recreational athletes or nonathletes; 29% were competitive athletes at a regional level, and 11% were competitive athletes at elite/national level. They were all referred to the Department of Orthopaedics at Sahlgrenska University Hospital (Gothenburg, Sweden) between January 2012 and October 2013 for suspected CACS. Nineteen healthy control subjects (10 women, 9 men) with no history of leg pain requiring medical attention were also included in the study.

Ethical Considerations

The study was approved by the regional research ethics committee. It was a part of a clinical routine investigation for patients with exercise-induced leg pain and suspected CACS. All control subjects gave their informed written consent prior to participation in the study.

Clinical Investigation and Exercise Test Protocol

Each patient underwent a clinical investigation by an orthopaedic surgeon before and after an exercise test. The test was individually designed to elicit each patient’s symptoms, and it often but not always included running on a treadmill or outdoors until the symptoms were provoked. This was always followed by maximum concentric dorsiflexion of the ankle joints in standing position to further provoke the symptoms. The control subjects performed only maximum concentric dorsiflexion to induce muscle fatigue in the tibialis anterior. The exercise continued until the participant (patient or control subject) was unable to continue because of pain and/or leg muscle fatigue.

Intramuscular Pressure Recording

The IMP was continuously monitored immediately (within 15 to 30 seconds) after the exercise test in the most symptomatic leg with the patient in a supine position. The amplitude was displayed on the monitor as the peak-to-peak value of the oscillations. The IMP was measured using the same procedure for the control subjects, but the test leg was randomly selected.

An 18-gauge (1.2 × 50 mm) needle with 4 side holes at the tip was introduced through the fascia of the anterior tibialis muscle in a distal direction at an angle of 30° from the plane of the skin, while the subject kept his or her ankle joint dorsiflexed. Once the needle penetrated the fascia, the subject was asked to relax, and the ankle joint was kept in a neutral position. The needle was then advanced 40 mm (insertion point to needle tip) as parallel as possible to the tibialis anterior muscle fibers to minimize trauma and discomfort.[21] No anesthetic was used.

Before insertion, the needle was connected to a transducer line (200 cm) filled with saline, which was linked to a pressure recording system (Hemo 4; Siemens) and a monitor (Siemens SC 9000; Siemens). A microcapillary infusion technique (1 mL/h) was used during insertion (the infused volume was <8 µL) to create a fluid pathway and establish needle patency. Needle patency and confirmation of the dynamic properties of the IMP recording system were checked by gentle external compression of the anterior tibialis muscle by the investigator’s fingertip.

The infusion of saline was stopped once the needle was located in the muscle, and it was kept closed during the measurements to avoid biased pressure readings due to volume load at the tip of the needle. This meant that the system was used as a noninfusion method. Calibration of the pressure recording system was performed before and after each measurement. The IMP and the pulse-synchronous oscillations were recorded continuously and displayed in real time on the monitor. During the IMP measurement, the heel was placed on a support to prevent external compression of the calf, and the foot was kept in a neutral relaxed position, as the position of the ankle affects the IMP.[5,19]

Criteria for CACS

The diagnostic criteria for CACS were history of exercise-induced leg pain, pain over the anterior compartment of the leg induced by the exercise test, and IMP at rest exceeding 30 mm Hg 1 minute after exercise and exceeding 20 mm Hg 5 minutes after exercise. All 4 criteria were required for the diagnosis of CACS.

Blood Pressure and Pulse Rate

Systolic and diastolic blood pressure and pulse rate were recorded in all participants by a manometer (NAIS; Matsushita Electronic Works), which was applied to the left forearm. Mean arterial pressure (MAP) was defined as diastolic pressure plus one-third of the pulse pressure (systolic minus diastolic). Local perfusion pressure for the anterior tibialis muscle was calculated as the difference between MAP and IMP.

Recording of Electromyographic Activity

The root mean square of the electromyographic (EMG) recordings from the anterior tibialis muscle was used to ensure muscle relaxation (no muscle activity) at rest after exercise, thereby preventing an erroneous diagnosis of CACS.[21] The EMG was recorded with disposable surface electrodes (Blue Sensor; Medicotest). The electrodes were placed 3 cm distal to the pressure needle tip. Cables were kept short to minimize noise. The signal was preamplified (gain, 100) close to the source, filtered with a second-order Butterworth filter with a passband of 10 Hz to 2 kHz, amplified with variable gain, and sampled at 4 kHz.

Statistics

Pressure values are presented as mean ± SD. Correlations are given with Pearson r. Differences between groups were determined with the Mann-Whitney U test. Significance was set at P < .05. To test the association between CACS and pulse-synchronous IMP oscillations, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the values collected 1 minute after exercise. A diagnosis of CACS was regarded as the reference standard. For the test, pulse-synchronous IMP oscillations with a peak-to-peak amplitude of >2 mm Hg were chosen as the cutoff value to indicate CACS.

Results

The mean age of the CACS patients was 29 years (range, 15-58 years), and the mean body mass index (BMI) was 27 kg/m2 (range, 20-40 kg/m2). For the non-CACS patients, the mean age was 34 years (range, 16-69 years) and BMI was 25 kg/m2 (range, 18-35 kg/m2). Among the control subjects, the mean age was 28 years (range, 20-42 years) and BMI was 24 kg/m2 (range, 20-34 kg/m2).

Based on clinical evaluation and the results of IMP measurements, 53 patients were diagnosed as having CACS and 36 patients had other causes of leg pain. The IMP at 1 minute postexercise was 54 ± 16 mm Hg (range, 30-88 mm Hg) in patients with CACS, 17 ± 6 mm Hg (range, 7-29 mm Hg) in non-CACS patients, and 18 ± 5.2 mm Hg (range, 9-27 mm Hg) in control subjects. The EMG signal at rest after exercise was silent in all participants, indicating that the measured IMP was not biased by leg muscle activity.

The amplitude of the IMP oscillations 1 minute postexercise was 7.1 ± 3 mm Hg (range, 2-15 mm Hg) in patients with CACS and 1.3 ± 0.9 mm Hg (range, 0-3 mm Hg) in non-CACS patients (P < .0001). It was 1.5 ± 0.6 mm Hg (range, 1-3 mm Hg) in control subjects. The amplitude of the IMP oscillations was significantly higher in CACS patients than in the control subjects (P < .0001), but no difference was found between non-CACS patients and control subjects (P = .61). The IMP and amplitude of the oscillations in CACS patients decreased gradually at rest after exercise (Table 1, Figures 1 and 2).

TABLE 1

IMP and IMP Oscillation Amplitude

Time, min	IMP		IMP Oscillation Amplitude
	Mean ± SD, mm Hg	No. of Patientsb	Mean ± SD, mm Hg	No. of Patientsb
1	54 ± 16	53	7.1 ± 2.9	53
2	51 ± 17	43	6.1 ± 2.8	43
3	46 ± 16	40	5.2 ± 3.0	40
4	43 ± 17	40	4.6 ± 2.7	40
5	41 ± 18	37	4.2 ± 3.2	37
6	38 ± 18	35	3.8 ± 3.2	35

Measurements were taken from 1 to 6 minutes after the cessation of an exercise test that reproduced symptoms in patients with chronic anterior compartment syndrome. IMP, intramuscular pressure.

Number of patients measured at each time point.

Figure 1.

(A) Abnormally elevated intramuscular pressure (IMP) at rest after exercise in a patient with chronic anterior compartment syndrome. The amplitude of the IMP oscillations decreased from 6 to <2 mm Hg, and the IMP decreased from 41 to 23 mm Hg over 5 minutes. (B) Close-up of the amplitude in the same patient at a time interval between 60 and 70 seconds.

Figure 2.

Mean amplitudes of the intramuscular pressure (IMP) oscillations and the corresponding mean IMP in patients with chronic anterior compartment syndrome measured at rest from 1 to 6 minutes after an exercise test that elicited the symptoms of leg pain. The numbers 1 to 6 represent the values at each minute.

The correlation (r = 0.60) between the IMP and the amplitude of the IMP oscillations recorded at 1 minute is shown in Figure 3. Postexercise IMP oscillations with an amplitude exceeding 2 mm Hg were highly associated with CACS, with a sensitivity of 96% and a specificity of 94%. The PPV and NPV were 96% and 94%, respectively.

Figure 3.

Correlation (r = 0.60) between the peak-to-peak amplitude of the intramuscular pressure (IMP) oscillations and the level of IMP 1 minute after an exercise test that elicited the symptoms in patients with chronic anterior compartment syndrome.

The CACS group comprised 43% women and 57% men, while the non-CACS group comprised 73% women and 27% men. The IMP was 48 ± 14 mm Hg for women and 59 ± 16 mm Hg for men in the CACS group (P < .01), while the amplitude of the IMP oscillations was 6.8 ± 2.7 mm Hg for women and 7.4 ± 3.1 mm Hg for men (P > .5).

Low local perfusion pressure correlated (r = 0.66) with high amplitudes of the IMP oscillations (Figure 4). In our analysis of the association between local perfusion pressure and the amplitude of IMP oscillations, we dichotomized the CACS patients into 2 groups, those with local perfusion pressures of <30 and >30 mm Hg. The local perfusion pressure was <30 mm Hg in 42% of the patients with CACS. The IMP in this group of patients was 69 ± 11 mm Hg, well below the mean arterial pressure. The amplitude of the IMP oscillations was 9 ± 3 mm Hg in this group. The local perfusion pressure exceeded 30 mm Hg in 58% of the patients with CACS. The corresponding IMP was 43 ± 9 mm Hg, and the amplitude of the IMP oscillations was 6 ± 2 mm Hg. The mean arterial pressure (Table 2) did not differ significantly between CACS and non-CACS patients (P > .7) or between CACS and control subjects (P > .2).

Figure 4.

Correlation (r = 0.66) between peak-to-peak amplitude of the intramuscular pressure (IMP) oscillations and local perfusion pressure in the anterior tibialis muscle at rest 1 minute postexercise in patients with chronic anterior compartment syndrome.

TABLE 2

Blood Pressure, Mean Arterial Pressure, Local Perfusion Pressure, and Pulse Measured 1 Minute After Exercise in Study Subjects

	Blood Pressure, mm Hg		Mean Arterial Pressure, mm Hg	Local Perfusion Pressure, mm Hg	Pulse, bpm
	Systolic	Diastolic
CACS patients	119 ± 11	71 ± 8	88 ± 9	34 ± 19	75 ± 15
Non-CACS patients	118 ± 11	74 ± 7	88 ± 7	71 ± 9	76 ± 16
Controls	118 ± 8	70 ± 6	86 ± 5	68 ± 6	65 ± 11

Values are reported as mean ± SD. CACS, chronic anterior compartment syndrome.

No complications of the IMP measurements were observed.

Discussion

This study shows that the amplitude of the pulse-synchronous IMP oscillations after exercise was significantly higher in patients with CACS compared with non-CACS patients and control subjects. Oscillations with an amplitude of >2 mm Hg 1 minute after exercise have a sensitivity of 96% and a specificity of 94% to identify CACS.

The observations of this study indicate that the amplitude of the pulse-synchronous IMP oscillations are correlated with increased IMP at rest after exercise in patients with CACS. The increased amplitude demonstrates the decreased compliance of the anterior compartment due to increased muscle swelling (volume load) immediately after exercise. This finding is supported by experimental evidence that shows that the arterial pulse transfers to the fascia and results in fascial motion in conditions of elevated IMP in simulated compartment syndrome.[4,10,20] Furthermore, an experimental study of abnormally elevated IMP in the human leg reported a high correlation between the level of IMP and the amplitude of pulse-synchronous IMP oscillations (Nilsson et al, unpublished data, 2014). These authors suggested that the amplitude of the pulse-synchronous IMP oscillations may be an additional pressure parameter in diagnosing both chronic and acute compartment syndromes. All of these studies thus indicate that the amplitude of pulse-synchronous IMP oscillations may be associated with the pathophysiological mechanisms of CACS.

A systematic review reported conflicting evidence regarding the validity of different IMP criteria in diagnosing CACS, including the absolute level of IMP at rest postexercise.[13] The absolute value of IMP depends on catheter depth,[11,14] the increased volume of the muscle during exercise,[17] the passive stretch of the muscle,[6] the degree of muscle activation at rest,[21] or a combination of all these factors. They all add to the diagnostic uncertainty of using only the level of IMP at rest in diagnosing CACS. The amplitude of the IMP oscillations at rest after an exercise test that elicits the symptoms may therefore be an additional parameter continuously validating the pressure recording system and supporting the results of IMP measurements.

To calculate sensitivity and specificity of the amplitude in diagnosing CACS, the cutoff value of the amplitude of the oscillations was set at 2 mm Hg. The cutoff value needs to differentiate the small IMP oscillations that may occur in a healthy muscle from those of CACS. In a human experimental study, no oscillations were seen at baseline when the IMP was 5 mm Hg, but the amplitude was 3.9 mm Hg when the IMP was elevated to 49 mm Hg by applying a simulated compartment syndrome model (Nilsson et al, unpublished data, 2014). Another study reported amplitudes of 5.8 ± 2.7 mm Hg in 36 CACS legs and amplitudes of <1 mm Hg or not detectable in 85 non-CACS legs at rest postexercise.[16] These reported results indicate that the amplitude is <2 mm Hg in non-CACS subjects. The role of the muscle fascia in generating low muscle compliance and high amplitudes of IMP oscillations was illustrated in a study that showed that surgical treatment by fasciotomy of patients with CACS reduces the oscillations from 4.9 ± 2.7 mm Hg before to 1.0 ± 0.6 mm Hg following surgery.[15] As a result, 2 mm Hg was selected as a cutoff value in the present study. This cutoff proved to have both high sensitivity and high specificity in identifying patients with CACS.

The local perfusion pressure was 34 mm Hg at 1 minute postexercise for the CACS patients compared with 71 mm Hg for the non-CACS patients and 68 mm Hg for the control group (see Table 2). This implies that the local perfusion pressure during the exercise test decreased to less than 50% in the patients with CACS. Low local perfusion pressure was correlated with high amplitudes of the IMP oscillations because the level of the local perfusion pressure is mediated by the IMP level. As expected, the amplitude of the IMP oscillations is not associated with the mean arterial pressure. However, the IMP in the CACS group was lower than the mean arterial pressure, so the amplitude of IMP oscillations remains to be investigated when the local perfusion pressure approaches 0 mm Hg. Garabekyan et al[4] found that the amplitude of the displacement of the muscle fascia decreased when the IMP was higher than the mean arterial pressure, indicating that, when the arterial flow into the compartment is restricted by the high IMP, less of the arterial pulse is transmitted to the surrounding tissue. If this also occurs when the local perfusion pressure is low but still positive, it may explain why one of our patients with a high IMP (low local perfusion pressure) had a small amplitude (3 mm Hg).

Experimental evidence from animal and human studies indicates that an elevated IMP may impede muscle capillary blood flow. A local perfusion pressure exceeding 30 mm Hg in nontraumatized muscle and 40 mm Hg in traumatized muscle is compatible with normal tissue metabolism.[9] Moreover, Hartsock et al[8] provided direct observations of the microcirculation of skeletal muscle under normal and increased compartment pressures. They demonstrated that an increasing IMP reduced the number of perfused capillaries per unit area and muscle capillary blood flow when the IMP was within about 25 mm Hg of the mean arterial pressure. Based on these observations, we dichotomized CACS patients according to the level of local perfusion pressure as <30 and >30 mm Hg. Our result clearly shows that the IMP oscillations were significantly higher in patients with perfusion pressure <30 mm Hg compared with patients with >30 mm Hg. This result is also in line with those of Garabekyan et al,[4] who reported that the amplitude of fascial displacement increased with reduced local perfusion pressure.

In this study, women were more likely to have causes for leg pain other than CACS. The total patient group comprised 55% women, and the non-CACS group comprised 73% women. To our surprise, the IMP was 11 mm Hg higher in men than in women in the CACS group. A sex difference of this magnitude has not previously been reported. The difference may be explained by many factors, including the intensity and duration of the exercises test. In the present study, the intensity and duration were participant selected and not controlled or measured. The amplitude of the IMP oscillations was more consistent and did not differ between men and women.

In rare cases, the IMP may be elevated initially at rest postexercise due to the patient’s inability to completely relax the leg extensor muscles because of leg pain.[21] This was ruled out in our study, as all participants had a silent EMG signal.

The purpose of using microcapillary infusion during the insertion of the needle was to ascertain that the tip of the needle was filled with fluid. Lack of fluid at the tip impairs the dynamic properties of the pressure recording system. The system was used as a noninfusion technique since the saline infusion was kept closed during the measurements to avoid biased pressure readings due to volume load in the muscle compartment.[17] The recording system needs a short time period to stabilize and equilibrate after the saline microinfusion is closed. Although the IMP was recorded continuously after needle insertion, the first IMP value considered valid for analysis was collected 1 minute after exercise.

One limitation in our study is that only patients with suspected CACS were included. It remains to be shown whether the 2 mm Hg cutoff value used in this study is the accurate limit for other compartments as well. Another limitation is that to test the sensitivity and specificity of the amplitudes of the IMP oscillations, our inclusion criteria including IMP measurement were used as a reference. Furthermore, our measurement system had a 1 mm Hg minimum resolution of the displayed IMP amplitude. The IMP values in patients with and without CACS were not compared statistically in our study, since the groups were defined by the IMP pressure criteria used in the study. Measurement of the amplitude does not impose any additional costs, extra effort, or time consumption since the oscillations are easily obtained during clinical routine IMP measurements.

Conclusion

The amplitude of pulse-synchronous IMP oscillations exceeding 2 mm Hg is a reliable parameter, with high sensitivity and specificity that supports the diagnosis of CACS. The parameter is easily obtained during routine IMP measurement and it is related to the pathophysiology of CACS. Continuous confirmation of catheter patency is ensured when oscillations of the IMP are recorded.