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Annals of Physical and Rehabilitation Medicine 55 (2012) 229240

Original article / Article original

Comparison of gaseous cryotherapy with more traditional forms of cryotherapy following total knee arthroplasty
rapie gazeuse a ` des formes de cryothe rapie plus Comparaison de la cryothe ` s arthroplastie totale du genou traditionnelles apre C. Demoulin a,*,b, M. Brouwers a, S. Darot a, P. Gillet c, J.-M. Crielaard a,b, M. Vanderthommen a,b
a

`ge University, Alle e des Sports 4, 4000 Liege, Belgium Department of Motricity Sciences and Rehabilitation, Lie b `ge University Hospital (CHU), Liege, Belgium Department of Physical Medicine and Rehabilitation, Lie c `ge University Hospital (CHU), Liege, Belgium Department of Orthopaedic Surgery, Lie Received 4 July 2011; accepted 13 March 2012

Abstract Objective. The aim of this study was to assess the efcacy of gaseous cryotherapy following total knee arthroplasty (TKA) and to compare it to routinely used strategies for applying cold therapy. Patients and methods. Sixty-six patients undergoing primary unilateral TKA were randomized into three groups and received gaseous cryotherapy (GC), cold pack and cryocuff applications, respectively throughout the hospital stay. Primary outcomes (knee pain intensity, mobility and girth measurements) were recorded on preoperative day 1 as well as on postoperative day (POD) 7. Cutaneous temperature of the knee sides were also measured on POD7 just before and immediately after cold application. Results. Although skin temperature dropped to 14 8C following GC versus 22 to 24 8C for the other two applications (P < 0,05), the three groups did not differ at POD7 regarding the three primary outcomes. No adverse effects were observed with any of the ways of application. Conclusions. Gaseous cryotherapy was not more benecial than routinely used strategies for applying cold therapy. Further studies with larger sample size and with a more frequent and closer gaseous cryotherapy applications are needed to conrm our results. # 2012 Elsevier Masson SAS. All rights reserved.
Keywords: Cryotherapy; Cold; Total knee replacement; Pain; Mobility

sume Re valuer lefcacite de la cryothe rapie gazeuse apre ` s prothe ` se totale de genou (PTG) et la comparer a ` des modalite s traditionnelles Objectif. E rapeutique du froid. dapplication the s pour une PTG unilate rale primaire ont e te randomise s en trois groupes qui ont be ne cie thodes. Soixante-six patients programme Patients et me rapie gazeuse (CG), dun cold pack et du cryocuff au cours de leur pe riode dhospitalisation. Lintensite de la respectivement de cryothe rime triques, et de mobilite du genou, qui constituaient les variables principales, ont e te enregistre es la veille de douleur et les mesures pe ` s lintervention (J + 7). La tempe rature cutane e du genou a e galement e te mesure e dans les trois lintervention chirurgicale ainsi que sept jours apre ` J + 7, juste avant et apre ` s lapplication du froid. groupes a rature cutane e ait chute jusqua ` 14 8C suite a ` la CG versus 22 a ` 24 8C pour les deux autres formes dapplication sultats. Bien que la tempe Re rimentaux ne diffe raient pas signicativement a ` J + 7 en termes dintensite de la douleur, de mobilite et de ( p < 0,05), les trois groupes expe rime triques. Aucun effet secondaire na e te observe au sein des trois groupes expe rimentaux. mesures pe rapie gazeuse ne sest pas re ve le e plus efcace que des modalite s traditionnelles dapplication the rapeutique du froid. Conclusions. La cryothe tudes comple mentaires sur des e chantillons plus larges, avec une application plus fre quente et une pulve risation plus proche, sont ne cessaires Des e sultats. pour conrmer ces re serve s. # 2012 Elsevier Masson SAS. Tous droits re
rapie ; Froid ; Prothe ` se genou ; Douleur ; Mobilite s : Cryothe Mots cle * Corresponding author. E-mail address: christophe.demoulin@ulg.ac.be (C. Demoulin). 1877-0657/$ see front matter # 2012 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.rehab.2012.03.004

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1. English version 1.1. Introduction Cold has been long known to have therapeutic effects: Hippocrates reported use of ice or snow to reduce edema formation and pain about 400 years before Christ [37]. Nowadays, it is extensively used and is considered to be a key treatment for various acute injuries. Use of cold therapy (cryotherapy) has long been empirical. Although several studies have been conducted on the topic, numerous questions and controversies remain regarding its effects and the optimal ways to use it [24]. Such discrepancies result from the signicant heterogeneity between studies, which prevents comparative study, and from the low number of controlled and randomized studies [5]. Literature [10,17,31] reports several physiologic effects of cryotherapy including reduction of skin [9,24], muscle [24] and articular [26,32] temperature, vasoconstriction of skin blood vessels [10] leading to decrease in blood ow [19], and reduction of the inammatory process resulting from decrease of tissue metabolism and from reduction in enzymatic activity [10]. Application of cold also induces analgesia by means of an anti-nociceptive effect on the gate control system and the decrease of nerve conduction speed [10,14] as well as prevention/reduction of post-traumatic edema and blood loss in post-surgical patients thanks to a decrease of vascular permeability and the vasoconstriction [17,40]. Various cooling mechanisms or devices used in clinics or on the sports eld have been reported in the literature [10,28]. Gaseous cryotherapy is one of them; this sophisticated cold application is based on the projection of CO2 microcrystals under high pressure [8,13,30] (CO2 is now used instead of nitrogen-cold air [33,34]). This technique is supposed to decrease skin temperature [30] to a greater extent than an ice bag and cause a more pronounced thermal shock; Mourot et al. also observed that gaseous cryotherapy triggered a systemic cutaneous vasoconstriction response [30]. According to Chatap et al., hyperbaric CO2 cryotherapy can also decrease pain scores in elderly inpatients with acute or chronic pain [8]. However, no other studies have investigated the clinical benets of hyperbaric gaseous cryotherapy. Thus, no published data are available regarding its benets following total knee arthroplasty (TKA), which is a frequent surgical option to treat patients with end-stage knee osteoarthritis (OA) [4,23]. Although cryotherapy is used most of the time in postsurgical patients, there is no consensus regarding the optimal method of application i.e. forms of cryotherapy, temperature and frequency application, etc. [1,3] and the specic management of cryotherapy after TKA [3]. The need for further research stated in a survey on current practice of cryotherapy after TKA [3] is conrmed by recent literature reviews on this topic [1,25]. Accordingly, the aim of the present work was to study whether gaseous cryotherapy is more effective in the postoperative care of people with TKA than routinely used cold application strategies i.e. cold gel packs or the Cryocuff1.

1.2. Patients and methods 1.2.1. Participants This prospective study concerned patients who were ` ge University undergoing primary unilateral (TKA) in the Lie Hospital. Patients were eligible for the study according to the following inclusion criteria: age between 40 and 85 years, severe osteoarthritis requiring a TKA. The exclusion criteria were: severe varus or valgus deformity, not procient in French, rheumatoid arthritis, as well as major associated medical problems such as peripheral vascular disease, associated acute pathology, cold urticaria, and Raynauds phenomenon. All patients received a low contact stress (LCS) prosthesis (De Puy, Johnson and Johnson) and were operated on by a senior orthopaedic surgeon with an anteromedial approach of the knee joint. A tourniquet was used in all patients and devascularisation of the leg lasted 45 to 55 minutes. All patients gave written informed consent to participate. ` ge University Hospital The medical ethics committee of the Lie approved the study protocol. 1.2.2. Experimental design/procedure On preoperative day 1 (PreOD1), patients were randomized into three groups using a computer generated table of random numbers; these groups differed by the main method that was going to be used to apply cold therapy throughout the hospital stay. In the gaseous cryotherapy group (GC), a CryotronTM dical, Salins-les-Bains, France) was used. device (Cryonic Me This device consists of medical-grade liquid CO2 in a cylinder equipped with an electrovalve and an immersed tube, a spray gun, and a nozzle. The CO2 is sprayed on dry skin over the knee using a slow, regular, sweeping movement. A pistol tted with a laser-guided infrared measurement system allows to control instantaneously the degree of skin cooling. A light switches on when the skin temperature drops to about 4 8C in order to avoid a risk of frostbite. As recommended by the manufacturer, the tip of the nozzle was kept 15 to 20 cm away from the skin. Gaseous cryotherapy provides painless (dry gas) air under high pressure (50 Bar) at a very low temperature (78 8C) which causes the skin temperature to fall very quickly. Hyperbaric CO2 cryotherapy was applied to patients for 90 seconds (30 seconds over the internal side of the knee, 30 seconds over the other side and 30 seconds over the popliteal fossa). The CO2 was sprayed three times per day. In the cold pack group (CP), a traditional gel pack (Physiopack1) (width 13 cm, length 30 cm, weight 400 g) was frozen for a minimum of 2 hours before application. The gel pack was placed transversally over the knee and secured with an elastic wrap. A towel was used as a barrier to prevent frostbite. The gel pack was applied to patients for 20 minutes, ve times a day. The cryocuff group (CC) was treated with a watercirculating device (Aircast1 Cryocuff1, Inc., Summit, New Jersey) combined to the AutoChill1 System (Aircast1, Inc., Summit, New Jersey) to provide cold and focal compression. A specic cuff surrounding the knee with pressurized ice water is

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linked by a tube to a cooler holding water and ice. It was applied to the knee for 20 minutes, ve times a day. All patients received cold therapy starting from postoperative day (POD) 2 (an earlier application was not possible because of the thickness of the dressings) and the therapy continued until the last hospitalization day. In all the groups, the applications were spaced by at least 1 hour: the rst two cold applications were done in the morning (respectively before the physiotherapy session and before lunch) whereas the others took place in the afternoon. All patients were treated by the same physical therapist; they also received physiotherapy (30 min/day) which included traditional exercises including knee mobilization, muscle strengthening and gait training. On Saturdays and Sundays, patients of the GC and CC groups were not treated with gaseous cryotherapy or with the Cryocuff1: a gel pack identical to the CP group was applied to them. 1.2.3. Outcomes Data were recorded on PreOD1 as well as on POD7 (corresponding to the minimal hospitalization length of stay); measurements took place in the morning, before cold application. The primary outcomes were the following:  pain intensity. We used a visual analog scale (VAS) to measure knee pain intensity. The scale was a 10 cm line with no graduations that had the words no pain at one end and worst pain imaginable at the other end. The patient was asked to answer the following question: How intense is your pain in the knee now? by making a vertical mark on the line at the place that best reected the intensity of the pain. The distance between the left end of the line (no pain) and the mark in millimeters was the VAS pain score (range 0100);  swelling of the phatologic knee and of the contralateral (control) knee was measured by bilateral girth measurements. They were taken with a meter tape at three levels i.e. at the joint line, 5 cm below it and 10 cm above it;  passive and active knee exion and extension range of motion were measured in a supine position using a goniometer. Its axis was placed over the lateral femoral epicondyle. The proximal end of the goniometer was aligned with the greater trochanter of the femur and the distal arm was aligned with the lateral malleolus. Measurements were recorded with respect to full extension being 0 degree with positive numbers indicating a more exed position and negative numbers

indicating hyperextension. During knee exion, subjects were instructed to maximally ex the hip and knee and draw the heel toward the buttocks. The cutaneous temperature of the internal and external sides of the knee was a secondary outcome; it was measured on POD7 just before and immediately after cold application as well as 30 minutes after application by using an infrared portable thermometer. 1.3. Statistics Means and standard deviations were calculated by using basic statistical analysis. The between-group comparisons (at baseline and at POD7) were performed by means of an analysis of variance (Anova). Variables changes between PreOD1 and POD7 and the differences between the non-operated and the operated knee were analyzed by means of a paired t-test; analysis of variance with repeated measurements was used to examine changes in cutaneous temperature. A per-protocol analysis was used. For all tests, a P-value 0.05 was considered statistically signicant. All statistical analyses were performed with SPSS software, version 16.0. 1.4. Results Forty female patients (mean standard deviation [SD]), 70.7 8.6 y; height, 162.3 7.8. cm; weight, 76.5 14.9 kg) and 26 male patients (70.1 8.5 y; height, 175.1 5.3 cm; weight, 81.3 10.1 kg) met the inclusion criteria and were selected for the current study. They all accepted to participate and were all submitted to the measurements during both evaluation sessions, i.e. PreOD1 and POD7. In terms of age, bodyweight and height, there was no signicant difference (P > 0.05) between groups (Table 1). The between-group comparisons at baseline revealed no signicant difference with regard to pain intensity. Following surgery, it increased signicantly in the CP (P < 0.05) and GC groups (P < 0.01) whereas it remained stable in the CC group (Fig. 1). At POD7, pain intensity was slightly higher in the CP group than in the other groups but the difference between groups remained non-signicant (P = 0.452). At PreOD1 and when pooling all patients (n = 66), the knee girth measurements were signicantly lower in the control

Table 1 Characteristics of the female and male patients of the three experimental groups i.e. gaseous cryotherapy (GC), cold pack (CP) and cryocuff (CC) groups. GC (n = 22) Males M SD n Age (years) Weight (kg) Height (cm) 8 71.5 6.5 78.6 5.4 173.1 3.6 Females M SD 14 72.3 7.7 79.2 19.2 163.4 6.4 CP (n = 22) Males M SD 9 67.2 11.9 77.7 11.2 175.2 6.8 Females M SD 13 68.8 9.5 75 15.4 162.8 10.2 CC (n = 22) Males M SD 9 71.7 5.6 87.3 10.3 176.8 4.9 Females M SD 13 70.9 8.8 75 8.2 160.7 6.5

M: means; SD: standard deviations.

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Fig. 1. Pain intensity in the knee recorded in the three groups (gaseous cryotherapy [GC], cold pack [CP] and cryocuff [CC] groups) on preoperative day 1 (PreOD1) as well as on postoperative day 7 (POD7). *P < 0.05; **P < 0.01.

knee than in the pathological knee at the joint line (P = 0.042) and 5 cm below it (P = 0.029), but not 10 cm above it (Table 2). Passive and active knee range of motion in exion and extension were signicantly reduced in the pathological knee (Table 2). Following surgery, range of motion of the operated knee further decreased (P < 0.05) in all groups (Fig. 2). There was no signicant difference between groups. Girth measurements of the operated knee increased following surgery; at POD7, they remained signicantly higher than baseline values (P < 0.001) for all measurement sites (Table 3). Statistical analysis revealed no signicant difference between groups. No signicant differences were observed between internal and external sides regarding skin temperature; accordingly, results of both sides were merged. Fig. 3 presents skin temperature at the knee side before and immediately after the application, as well as 30 minutes later for the three experimental groups. In each experimental group, temperature signicantly decreased following the application (P < 0.001) and returned to baseline values within 30 minutes postapplication. No between-group difference regarding skin
Table 2 Baseline girth measurements (means standard deviations) at three levels (at the joint line [JL], 5 cm below it and 10 cm above it) as well as mobility (passive and active knee range of motion in exion and extension) of the operative knee and the control knee in the entire population. Patients (n = 66) Control knee M SD Girth measurements JL (cm) JL 5 (cm) JL + 10 (cm) Mobility Active exion (8) Passive exion (8) Active extension (8) Passive extension (8) 39.7 4.8 35.8 4.1 43.9 6.4 121.5 11.4 126.1 11.7 0.9 3.6 1.5 4.4 Operative knee M SD 40.5 3.9 36.2 3.9 44.3 6 116.6 12.3 120.6 12.5 3.6 5.5 1.3 5.8 P-value

temperature was observed except following the application, when skin temperature was decreased in a greater extent when using gaseous cryotherapy than when using the other forms of cryotherapy (P < 0.05). We did not observe any adverse effects with any of the ways of application. 1.5. Discussion The aim of this study was to assess the efcacy of gaseous cryotherapy in the postoperative care of people with TKA; therefore, we compared it to the easiest and most traditional way to apply cold (gel pack) [3] as well as to the Cryocuff1 which has been used in several previous studies involving patients following TKA [16,18,21,22,39]. Selecting patients after TKA to study cryotherapy benets appears to be relevant because it is a well circumscribed intervention, which causes extensive tissue damage as well as severe postoperative pain and edema [6]. The absence of a control/placebo group can be explained by the fact that cryotherapy is well accepted in the postoperative management of knee surgery [36], considering the severe postoperative pain [15,29,35] and the signicant benet of cryotherapy in pain control observed in several studies [21,22,29,39]. Benets of cryotherapy following TKA was conrmed by Morsi who studied 30 patients undergoing staged bilateral TKA [29]. In every patient, one TKA had a continuous-ow cooling device for 6 days postoperatively (skin temperature kept at a mean of 78C for the rst 2 hours and at 128C after that) whereas the other TKA in the same patient was done 6 weeks later and had no cooling device. Morsi reported that pain intensity score as well as analgesic consumption were always greater in the control group [29]. In addition to the effect on nerve conduction speed [2,27], cold is supposed to inhibit swelling by reducing edema [12]. As far as we know, the present study is the rst one that assesses the efcacy of hyperbaric gaseous cryotherapy in the postoperative care of people with TKA. The literature includes only a few studies of its physiological and clinical effects [8,30]. The three experimental groups did not differ signicantly at POD7 regarding pain intensity, mobility and girth

0.042 0.029 0.6 < 0.001 < 0.001 < 0.001 < 0.001

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Fig. 2. Passive and active range of motion in exion and extension of the operative knee measured in the three groups (gaseous cryotherapy [GC], cold pack [CP] and cryocuff [CC] groups) on preoperative day 1 (PreOD1) as well as on postoperative day 7 (POD7). *P < 0.05; **P < 0.01; ***P < 0.001. Table 3 Girth measurements (means standard deviations) of the operative knee at three levels (at the joint line (JL), 5 cm below it and 10 cm above it) in the three groups (gaseous cryotherapy [GC], cold pack [CP] and cryocuff [CC] groups) on preoperative day 1 (PreOD1) as well as on postoperative day 7 (POD7). GC PreOD1 M SD JL (cm) JL 5 (cm) JL 10 (cm) 40.2 4 35.2 3.3 43.1 6.2 POD7 M SD 43 4.5 37.6 3.3 46.8 5.7 P-value < 0.001 < 0.001 < 0.001 CP PreOD1 M SD 41 4.7 36.8 5 44.6 6.6 POD7 M SD 43.5 4.5 38.8 4.5 47.9 5.9 P-value < 0.001 < 0.001 < 0.001 CC PreOD1 M SD 40.3 3.1 36.2 3.1 44.5 4.7 POD7 M SD 42.9 3.4 38.9 3.6 47.4 4.8 P-value < 0.001 < 0.001 < 0.001

measurements. Changes from PreOD1 to POD7 were also identical between groups except for pain intensity, which remained stable only in the CC group; the latter observation might result partly from slightly higher baseline pain values in this group compared to the others. Consistent with the literature [21,22] mobility, which usually decreases drastically 1 day after surgery [21], was still reduced at POD7 as a result of swelling,

pain and muscle spasm [21]. At POD7, girth measurements (reecting swelling resulting from haemorrhage and edema [17]) remained also signicantly higher than baseline values in all the groups. Thus, clinical results were similar between groups although gaseous cryotherapy was applied only three times for 90 seconds whereas the cold pack and Cryocuff1 were used

Fig. 3. Skin temperature at the knee side before and immediately after the application, as well as 30 minutes later in the three experimental groups (gaseous cryotherapy [GC], cold pack [CP] and cryocuff [CC] groups). Different letters (a, b, c) represent signicant differences (P < 0.05).

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ve times a day for 20 minutes. Skin temperature resulting from such cold applications also differed considerably: baseline skin temperature was similar in the three groups (averaging 34 358C) and decreased signicantly in all groups when cold was applied; however, it reached 22 to 248C at the end of the cold pack or cryocuff applications and dropped to a mean of 148C following the gaseous cryotherapy. This more important thermal shock (fast decline in temperature), also reported by Mourot et al., results from the sublimation of dry ice to carbon dioxide gas which is a very endothermic reaction [30]. Mourot et al. reported a skin temperature reaching 7.38C at the end of a 2-minute gaseous cryotherapy application when maintaining the pipe at a distance of 7 to 10 cm of the skin surface of the dorsal aspect of one hand [30]. Therefore, a greater thermal shock might have occurred in our study if a longer application time and/or a closer application of gaseous cryotherapy had been applied. In this context, better clinical effects might also have occurred because decreased pain perception, reduction of edema, diminished metabolic enzyme activity, vasoconstriction are supposed to occur when skin temperature is reduced to about 108C to 158C [7,17,20,24,27]. As previously stated, the current study does not suggest difference between techniques regarding the clinical efciency; therefore the specic advantages and drawbacks of each modality should be taken into account when a choice between techniques has to be made. Gaseous cryotherapy provides similar benets to the more traditional cooling methods with lesser and shorter sessions; however a specic training for application is needed and the device (as well as the cylinders of gas) is costly. The traditional cold pack is very easy to use, even for patients, and is not expensive; however, the often-limited exibility of the frozen cold pack decreased the size of the contact area. The Cryocuff1 is easy to use, combines cryotherapy and compression [3], has been especially developed to conform well to the tissue and allows to keep a stable temperature for a longer time than with a cold pack; however it is more expensive than a cold pack and its combination to the AutoChill1 System (to provide continuous cold and pulsating pressure) requires electrical power. This present study suffers a few limitations. Our data were analyzed only on a per-protocol basis and the randomisation of our sample into three experimental groups decreases the statistical power of the present work. The hyperbaric gaseous cryotherapy, the Cryocuff1, as well as the cold pack secured with a wrap provided some compression, which might inuence positively the outcomes; results of studies comparing cold compression therapy with either modality alone remain controversial [5,6,16]. Furthermore, in the CC and GC groups, the Cryocuff1 and the CryotronTM were not used during the weekend (patients had a similar treatment as the CP group); although the methodology used in the current study best reects the clinical practice of our hospital (during the weekend, only the nurses are treating the patients), it might underestimate the benets of gaseous cryotherapy over the cold pack application. Considering our experimental design, we did not report the outcomes time course and based our results only on the POD7. Yet, measurements of pain intensity one day following the

surgery would have been useful in better interpreting the changes of this outcome. Although benets of cryotherapy on length of stay have been reported in previous studies [21,38], we did not consider this outcome. Indeed the discharge decision is inuenced by several factors, i.e. the future (hospitalisation in an inpatient rehabilitation service, in a day hospital or at the patients home), the achievement of functional independence (transfers, ambulation) and the living situation (alone or not, presence of a home help) of the patient [11,21]. 1.6. Conclusion No difference between groups was observed regarding the clinical outcomes. Further studies with larger sample size and with a more frequent and closer gaseous cryotherapy applications are needed to conrm that gaseous cryotherapy is not more benecial than more traditional cold applications following TKA. Disclosure of interest The authors declare having no private or personal interest to inuence the results of the present study. A commercial society lent the CryotronTM device for a denite period of time and gave several cylinders of compressed medical-grade carbon dioxide gas to conduct the study. Acknowledgments The authors acknowledge the valuable help and assistance of ` res, Mr Ms Annie Depaifve, Mr Paul Remont, Mr Richard Fre bastien Wolfs as well as Mr Andre Tits. Se 2. Version franc aise 2.1. Introduction rapeutiques du froid sont connus depuis Les effets the ja ` de longtemps : 400 ans avant JC, Hippocrate parlait de lutilisation de la glace ou de la neige pour reduire la formation ` mes et soulager la douleur [37]. des de et conside re De nos jours, le froid est couramment utilise dans de nombreuses blessures et comme un traitement cle rapie par le froid (cryothe pathologies. Lutilisation de la the te empirique. Bien que de nombreuses rapie) a longtemps e tudes se soient inte resse es au sujet, plusieurs questions et e controverses restent en suspens au sujet de ses effets et dapplication [24]. Cela concernant la meilleure modalite sulte de lhe te roge ne ite des travaux, empe chant toute e tude re tudes contro le es et comparative ainsi que du faible nombre de es [5]. randomise rature [10,17,31] rapporte plusieurs effets physioloLa litte rapie telles quune baisse de la tempe rature giques de la cryothe e [9,24], musculaire [24] et articulaire [26,32], une cutane s [10] de bouchant sur une vasoconstriction des vaisseaux cutane bit sanguin [19] et une re duction du processus baisse du de ce a ` une diminution du me tabolisme tissulaire inammatoire gra

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enzymatique [10]. Lapplication de froid et de lactivite ne e galement une analge sie par le le vation du seuil de la entra douleur et le ralentissement de la conduction nerveuse [10,14] vention/re duction des de ` mes post-traumaainsi que la pre re en raison de tiques et de la perte sanguine chez le patient ope abilite vasculaire et de la la diminution de la perme rature rapporte divers sysvasoconstriction [17,40]. La litte ` mes ou appareils de refroidissement utilise s dans les cliniques te rapie gazeuse est ou sur les terrains de sport [10,28]. La cryothe e une de ces techniques ; cette application de froid sophistique e sur la sublimation de CO2 liquide qui, a ` laide dun est base pistolet, permet la projection de microcristaux de carboglace s a ` une pression hyperbare [8,13,30] (le CO2 a remplace associe tait utilise initialement [33,34]). Cette lazote liquide qui e e a ` re duire brutalement la tempe rature technique est destine e [30] cre ant ainsi un choc thermique bien plus cutane quavec une poche de glace ; Mourot et al. ont note prononce rapie gazeuse de clenchait une re action syste que la cryothe e [30]. Selon Chatap et al., la mique de vasoconstriction cutane rapie hyperbare au CO2 permet e galement de re duire les cryothe ge s hospitalise s souffrant scores de la douleur chez les patients a s ou chroniques [8]. Cependant, aucune autre de douleurs aigue tude ne sest inte resse e aux be ne ces cliniques de cette e rapie gazeuse hyperbare. Ainsi, aucune donne e nest cryothe ne ces de cette technique apre `s disponible sur les be arthroplastie totale du genou, intervention chirurgicale pourtant quente en cas de gonarthrose avance e [4,23]. Bien que la fre rapie soit utilise e le plus souvent en postope ratoire, il cryothe thode optimale nexiste aucun consensus concernant la me rature cutane e a ` dapplication (choix de la technique, tempe quence dapplication [1,3]) ainsi que sur les atteindre, fre s dapplication spe ciques de la cryothe rapie apre `s modalite arthroplastie totale du genou [3]. Un sondage concernant les rapie apre ` s prothe ` se pratiques cliniques usuelles de la cryothe totale du genou (PTG) a souligne la necessite de mener des tudes comple mentaire sur le sujet [3] ; cette ne cessite ae te e conrmee par de recentes revues de litterature sur ce sujet tude e tait [1,25]. Pour ces raisons, lobjectif de cette e dexaminer si la cryotherapie gazeuse est plus efcace dans ratoire des patients ope re s dune PTG la prise en charge postope rapie plus couramment utilise es que les techniques de cryothe cold pack ou comme les poches de gel congele le Cryocuff1 . thodes 2.2. Patients et me 2.2.1. Participants tude prospective concernait des patients de lho pital Cette e ` ge programme s pour une PTG. Les crite ` res universitaire de Lie taient : a ge entre 40 et 85 ans, gonarthrose se ve ` re dinclusion e cessitant une PTG. Les crite ` res dexclusion e taient les ne formation importante en varus ou valgus, suivants : de hension limite e du franc de compre ais, polyarthrite rhumato es, comme une maladie ainsi que certaines conditions associe riphe rique (MVP) ou des pathologies se rieuses, vasculaire pe lurticaire au froid et la maladie de Raynaud. Tous les patients te ope re s par un chirurgien orthope dique se nior. La voie ont e

te ante ro-me diane et une prothe ` se LCS (De dabord a toujours e matiquement e te utilise e. Puy, Johnson and Johnson) a syste roule e sous garrot pneumatique avec un Lintervention sest de vascularisation de 45 a ` 55 minutes. Tous les sujets temps de de un formulaire de consentement e claire . Le comite ont signe thique de lho pital universitaire de Lie ` ge a approuve le de tude. protocole de dure 2.2.2. Protocole et proce te La veille de la chirurgie (J 1), les patients ont e s en trois groupes selon une liste informatise e de randomise rence entre les groupes nombre pris au hasard ; la seule diffe tant la me thode de cryothe rapie a ` utiliser au cours de e lhospitalisation. rapie gazeuse (CG), un Dans le groupe cryothe dical, Salins-les-Bains, France) a CryotronTM (Cryonic Me te utilise . Cet appareil contient du CO2 me dical liquide dans e quipe dune e lectrovalve et dun tube immerge , un cylindre e sur la peau dun pistolet et dun embout. Le CO2 est projete ` che au niveau du genou avec un mouvement de balayage lent se gulier. Le pistolet e quipe avec un syste ` me de capteur de et re ` infrarouge, guide par laser, permet de contro ler mesure a ment le degre de refroidissement de la peau. Une instantane ` re sallume quand la tempe rature de la peau atteint 4 8C lumie viter le risque dengelures. Suivant les recommandaan de tait tenu a ` distance de 15 a ` 20 cm tions du fabricant, lembout e rapie gazeuse permet de pulve riser de de la peau. La cryothe ` haute pression (50 Bar) et a ` tempe rature tre ` s basse lair a ` s rapide de la tempe rature (78 8C) ce qui cause une chute tre rapie gazeuse hyperbare e tait applique e de la peau. La cryothe aux patients pendant 90 secondes (30 secondes sur la face te et 30 secondes sur interne du genou, 30 secondes de lautre co ` le creux poplite) a raison de trois fois par jour. Dans le groupe cold pack (CP), une poche de gel traditionnelle (Physiopack1) (largeur 13 cm, longueur 30 cm, tait mise au conge lateur au minimum 2 heures poids 400 g) e tait avant lapplication. La poche de gel recouvrait le genou et e ` re xee avec une bande elastique. Une serviette servait de barrie an deviter les engelures. Cette poche de froid etait utilisee sur les patients 20 minutes, cinq fois par jour. tait traite avec un syste ` me de Le groupe cryocuff (CC) e rapie base sur la circulation deau froide (Aircast1 cryothe a ` lAutoChill1 Cryocuff1, Inc., Summit, New Jersey) associe 1 System (Aircast 4, Inc, Summit, New Jersey) an dassurer e. Un manchon spe cique une compression froide et localise en eau glace e par une glacie ` re entourant le genou est alimente tait applique contenant de leau et de la glace. Ce manchon e ` raison de cinq fois par jour. pendant 20 minutes, a rapie commenc Pour tous les patients, la cryothe ait le ` me jour postope ratoire (J + 2) (une application plus to t deuxie tait difcile en raison de le paisseur du pansement) et la the rapie e continuait jusquau dernier jour dhospitalisation. Dans tous les taient espace es dau moins une heure : groupes, les applications e ` res avaient lieu le matin (respectivement avant la les deux premie ance de kine sithe rapie et avant le de jeuner) alors que les autres se ` s-midi. Tous les patients e taient traite s par le avaient lieu lapre me kine sithe rapeute ; ils be ne ciaient e galement de se ances me

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sithe rapie (30 minutes par jour) comprenant des exercices de kine traditionnels (mobilisation du genou, renforcement musculaire et nement a ` la marche). entra Le samedi et le dimanche, les patients des groupes CG et CC ne ciaient pas de cryothe rapie gazeuse ou du Cryocuff1 : ne be ` celle du groupe CP e tait utilise e. une poche de gel identique a 2.2.3. Variables te effectue es a ` J 1 et J + 7 (corresponLes mesures ont e ` dant a la duree dhospitalisation minimale) ; les mesures se faisaient le matin, avant lapplication du froid. Les variables taient : principales e de la douleur, e value e au moyen dune e chelle  lintensite visuelle analogique (EVA). Lechelle se presente comme une ligne sans graduation de 10 cm avec les mots aucune ` lextre mite gauche et pire douleur imaginable douleur a ` pondre a ` la question a lextremite droite. Le patient devait re de votre douleur au genou en suivante : quelle est lintensite chelle an de ce moment ? et il devait indiquer un trait sur le ter le plus pre cise ment lintensite de sa douleur. La ree te gauche (aucune douleur) et la marque distance entre le co ` tres) e tait de nie comme le faite par le patient (en millime ` 100) ; score EVA (de 0 a  le gonement du genou pathologique et celui du genou ral ( contro le ) e tait e value a ` laide de mesures controlate rime triques bilate rales. Ces mesures e taient effectue es a ` pe ` tre ruban en trois endroits : linterligne laide dun me articulaire, 5 cm en dessous et 10 cm au-dessus ;  lamplitude articulaire passive et active en exion et taient prises a ` laide extension du genou ; ces mesures e ` tre avec le patient en position allonge e. Laxe dun goniome ` tre e tait place au niveau du condyle fe moral du goniome ral. Lextre mite proximale du goniome ` tre e tait aligne e le late le long de long du grand trochanter et le bras distal positionne ole externe. Ze ro degre correspondait a ` une extension la malle ` te ; les nombres positifs indiquaient un exum de comple gatifs soulignaient une hyperextengenou et les nombres ne sion. Durant la exion du genou, les sujets avaient pour chir au maximum la hanche et le genou et instruction de e damener le talon vers les fesses. rature cutane e de la peau mesure e a ` la face interne La tempe et externe du genou constituait une variable secondaire ; cette

tait enregistre e a ` J + 7 juste avant et imme diatement mesure e ` s lapplication de froid, mais e galement 30 minutes apre `s apre ` tre portable a ` infrarouge. lapplication en utilisant un thermome 2.3. Statistiques carts-types (ET) ont e te calcule s a ` laide Les moyennes et e thodes danalyse statistique commune ment utilise es. Les de me ` linclusion et a ` J + 7) ont e te comparaisons intergroupes (a alise es avec une analyse de variance (Anova). Le volution des re variables entre J 1 et J + 7 et la comparaison des mesures du re et du genou contro le ont e te e tudie es au moyen genou ope ; une analyse de variance avec des mesures dun test-t apparie pe te es a servi a ` comparer la tempe rature cutane e mesure es a ` re rents. Une analyse per-protocole a e te trois moments diffe conduite. tait conside re e Pour tous les tests, la valeur p 0,05 e te comme statistiquement signicative. Toutes les analyses ont e alise es avec le logiciel SPSS, version 16.0. re sultats 2.4. Re te inclus. Quarante femmes Au total, 66 patients ont e cart-type, a ge 70,7 8,6 ans ; taille 162,3 (moyenne e ge 70,1 7,8.cm ; poids 76,5 14,9 kg) et 26 hommes (a 8,5 ans ; taille, 175,1 5,3 cm ; poids 81,3 10,1 kg). Ils ont de participer et ont e te e value s a ` deux reprises, tous accepte ` -dire J 1 et J + 7. En termes da ge, de poids et de taille, cest-a rence signicative ( p > 0,05) entre les il ny avait aucune diffe groupes (Tableau 1). ` linclusion nont mis en Les comparaisons intergroupes a vidence aucune diffe rence signicative au niveau de e de la douleur. Apre ` s la chirurgie, la douleur e tait lintensite e dans les groupes CP ( p < 0,05) et signicativement majore CG ( p < 0,01) alors quelle demeurait stable dans le groupe ` J + 7, lintensite de la douleur e tait le ge ` rement CC (Fig. 1). A leve e dans le groupe CP que dans les autres groupes, mais plus e rence entre les groupes ne tait pas signicative la diffe ( p = 0,452). ` J 1, les mesures pe rime triques des patients (n = 66) A taient signicativement re duites pour le genou contro le par e rapport au genou pathologique au niveau de linterligne articulaire ( p = 0,042) et 5 cm plus bas ( p = 0,029), mais pas 10 cm plus haut (Tableau 2).

Tableau 1 ristiques des patients masculins et fe minins au sein des trois groupes expe rimentaux (cryothe rapie gazeuse [CG]), cold pack [CP] et cryocuff [CC]). Caracte CG (n = 22) Hommes M ET n ge (anne e) A Poids (kg) Taille (cm) 8 71,5 6,5 78,6 5,4 173,1 3,6 Femmes M ET 14 72,3 7,7 79,2 19,2 163,4 6,4 CP (n = 22) Hommes M ET 9 67,2 11,9 77,7 11,2 175,2 6,8 Femmes M ET 13 68,8 9,5 75 15,4 162,8 10,2 CC (n = 22) Hommes M ET 9 71,7 5,6 4 87,3 10,3 176,8 4,9 Femmes M ET 13 70,9 8,8 75 8,2 160,7 6,5

cart-type. M : moyenne ; ET : e

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de la douleur pour chacun des trois groupes (cryothe rapie gazeuse [CG], cold pack [CP] et cryocuff [CC]) la veille de lintervention (J 1) ainsi que Fig. 1. Intensite ` s la chirurgie (J + 7). *p < 0,05 ; **p < 0,01. sept jours apre

Les amplitudes articulaires passives et actives en exion et taient nettement re duites pour le genou pathologiextension e que (Tableau 2). ` s lope ration, lamplitude articulaire du genou ope re Apre tait diminue e ( p < 0,05) dans tous les groupes (Fig. 2). e rence signicative ne tait note e entre les groupes. Aucune diffe rime triques du genou ope re e taient plus Les mesures pe leve es a ` J + 7 qua ` linclusion ( p < 0,001) et ce, pour tous les e points de mesure (Tableau 3). Lanalyse statistique na mis en vidence aucune diffe rence signicative entre les groupes. e rence signicative na e te observe e entre les faces Aucune diffe rature cutane e ; interne et externe du genou au niveau de la tempe quence, nous avons calcule et pre sente la tempe rature en conse e moyenne des deux faces. La Fig. 3 pre sente les cutane ratures cutane es au niveau du genou observe es dans les tempe rimentaux avant et imme diatement apre `s trois groupes expe lapplication du froid, mais egalement 30 minutes plus tard. Dans rature e tait signicativement plus basse chaque groupe, la tempe ` apres lapplication ( p < 0,001) avec un retour aux valeurs rence initiales dans les 30 minutes post-application. Aucune diffe intergroupe na ete relevee en ce qui concerne la temperature e, excepte imme diatement apre ` s lapplication de la cutane
Tableau 2 rime triques a ` linclusion (moyenne e cart-type) a ` trois niveaux Mesures pe (interligne articulaire [IA], 5 cm en dessous et 10 cm au-dessus) et mobilite initiale (amplitude articulaire active et passive en exion et extension) du genou re et du genou controlate ral (contro le) pour tous les patients. ope Patients (n = 66) le Genou contro M ET rime triques Mesures pe IA (cm) IA 5 (cm) IA + 10 (cm) Mobilite Flexion active (8) Flexion passive (8) Extension active (8) Extension passive (8) 39,7 4,8 35,8 4,1 43,9 6,4 121,5 11,4 126,1 11,7 0,9 3,6 1,5 4,4 re Genou ope M ET 40,5 3,9 36,2 3,9 44,3 6 116,6 12,3 120,6 12,5 3,6 5,5 1,3 5,8 0,042 0,029 0,6 < 0,001 < 0,001 < 0,001 < 0,001 Valeur p

` cet instant, la tempe rature e tait rapie ; en effet, a cryothe rablement plus basse apre ` s cryothe rapie gazeuse quapre `s conside rapie ( p < 0,05). lutilisation des autres formes de cryothe sirable na e te rapporte pour aucune des Aucun effet inde formes dapplications. 2.5. Discussion tude e tait de valuer lefcacite de la Lobjectif de cette e rapie gazeuse dans les soins postope ratoires des cryothe ` s une PTG ; ainsi, nous lavons compare e a ` la personnes apre rapie (poche de fac on la plus traditionnelle dutiliser la cryothe ) [3] et avec les manchons Cryocuff1 utilise s dans gel congele tudes sur des patients ope re s dune PTG plusieurs e lectionner ce type de patients [16,18,21,22,39]. Le choix de se tudier les be ne ces de la cryothe rapie nous a semble pour e pertinent car cette operation est bien denie et elle entrane des sions tissulaires conside rables avec de ` me se ve ` re et douleurs le importantes [6]. Labsence dun groupe temoin/placebo peut rapie est une the rapie bien sexpliquer par le fait que la cryothe ` acceptee dans les soins postoperatoires apres chirurgie du ratoire genou [36], compte tenu de limportante douleur postope [15,29,35] ; de plus, les beneces signicatifs de la rapie sur le contro le de la douleur sont rapporte s dans cryothe tudes [21,22,29,39]. Lefcacite de la cryothe rapie plusieurs e ` s PTG a e te conrme e par Morsi dans une e tude sur apre 30 patients ayant subi deux interventions chirurgicales (PTG rale) [29]. Pour chaque patient, les soins postope ratoires bilate ` re PTG consistaient en un syste ` me de pour la premie pendant les six jours postrefroidissement continu applique ratoires (tempe rature cutane e maintenue en moyenne a ` 7 8C ope ` res deux heures postope ratoires et a ` 12 8C par la pour les premie suite) ; la seconde intervention avait lieu six semaines plus tard, rapie postope ratoire. Morsi a montre que les mais sans cryothe taient scores de la douleur ainsi que la prise dantalgique e matiquement plus e leve s sans lutilisation de la cryothe syste rapie [29]. Outre ses effets sur la vitesse de conduction nerveuse duisant lde ` me [12]. [2,27], le froid inhibe le gonement en re ` notre connaissance, cette e tude est la premie ` re a `e valuer A de la cryothe rapie hyperbare dans la prise en charge lefcacite ratoire des PTG. La litte rature ne contient que peu postope

cart-type. M : moyenne ; ET : e

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re mesure e la veille de lintervention (J 1) ainsi que sept jours apre ` s la chirurgie Fig. 2. Amplitude articulaire passive et active en exion et extension du genou ope rapie gazeuse [CG], cold pack [CP] et cryocuff [CC]). *p < 0,05 ; **p < 0,01 ; ***p < 0,001. (J + 7) dans les trois groupes (cryothe Tableau 3 rime triques (moyenne e cart-type) a ` trois niveaux (interligne articulaire (IA), 5 cm en dessous et 10 cm au-dessus) dans les trois groupes (cryothe rapie Mesures pe ration (J 1) ainsi qua ` J + 7. gazeuse [CG], cold pack [CP] et cryocuff [CC]) la veille de lope CG J1 IA (cm) IA 5 (cm) IA 10 (cm) 40,2 4 35,2 3,3 43,1 6,2 J+7 43 4,5 37,6 3,3 46,8 5,7 p < 0,001 < 0,001 < 0,001 CP J1 41 4,7 36,8 5 44,6 6,6 J+7 43,5 4,5 38,8 4,5 47,9 5,9 p < 0,001 < 0,001 < 0,001 CC J1 40,3 3,1 36,2 3,1 44,5 4,7 J+7 42,9 3,4 38,9 3,6 47,4 4,8 p < 0,001 < 0,001 < 0,001

tudes sur les effets physiologiques et cliniques de cette de ` J + 7, aucune diffe rapie [8,30]. A rence forme de cryothe risignicative na ete observee entre les trois groupes expe mentaux en termes dintensite de douleur, de mobilite et de rime triques. Les changements entre J 1 et mesures pe ` J + 7 etaient egalement identiques entre les groupes, a lexception de lintensite de la douleur qui restait stable uniquement dans le groupe CC ; cette observation peut

sexpliquer en partie par les valeurs initiales de ce groupe qui taient le ge ` rement plus e leve es que celles des deux autres e es de la litte rature [21,22], la groupes. Conformement aux donne ` s la mobilite, qui diminue considerablement un jour apre ` ` chirurgie [21], etait encore reduite a J + 7 a cause du gonement, ` J + 7, les de la douleur et des spasmes musculaires [21]. A ` morragie mesures perimetriques (reetant le gonement lie a lhe ` et ldeme [17]) restaient egalement signicativement plus

rature cutane e du genou avant et imme diatement apre ` s lapplication, ainsi quau suivi a ` 30 minutes dans les trois groupes (cryothe rapie gazeuse [CG], Fig. 3. Tempe rents (a, b, c) repre sentent des diffe rences signicatives ( p < 0,05). cold pack [CP] et cryocuff [CC]). Des code-lettes diffe

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leve es qua ` linclusion pour tous les groupes. Ainsi, les re sultats e taient similaires entre tous les groupes, bien que la cliniques e rapie gazeuse ait e te uniquement applique e trois fois cryothe e de 90 secondes, alors que la poche de glace et pendant une dure taient utilise s cinq fois par jour pendant le Cryocuff1 e rature cutane e, apre ` s application du froid, 20 minutes. La tempe rablement : les valeurs initiales e taient similaires variait conside ` 35 8C) et dans les trois groupes (avec une moyenne de 34 a diminuaient de fac on importante dans tous les groupes quand le tait applique ; cependant, cette tempe rature atteignait 22 a ` froid e ` s lapplication de la poche de glace ou du Cryocuff1, 24 8C apre ` s la cryothe rapie gazeuse, celle-ci tombait a ` 14 8C alors quapre en moyenne. Ce choc thermique (baisse brutale de la rature) plus important, e galement rapporte par Mourot tempe sulte dune sublimation des cristaux de carboglace en un et al., re clenchant une re action endothergaz de dioxyde de carbone de tude, Mourot et al. ont mique importante [30]. Dans leur e une tempe rature atteignant 7,3 8C a ` la n des rapporte rapie en maintenant deux minutes dapplication de la cryothe ` une distance de 7 a ` 10 cm de la surface de la peau du lembout a dessus de la main [30]. Ainsi, on peut supposer quun choc tude si thermique plus important aurait pu avoir lieu dans notre e te plus longue et/ou si la cryothe rapie avait lapplication avait e te projete e plus pre ` s de la peau. Dans ce contexte, des effets e cliniques plus importants auraient pu intervenir, puisque la duction de la douleur, de lde ` me et de lactivite me tabolique re s a ` la vasoconstriction apparaissent norenzymatique associe rature cutane e tombe approximativemalement quand la tempe ` 10 8C [7,17,20,24,27]. ment a tude ne montre aucune diffe rence entre les Notre e rentes techniques en ce qui concerne lefcacite diffe ciques et clinique ; cest pourquoi les avantages spe savantages de chaque modalite the rapeutique doivent e tre de pris en compte au moment du choix des techniques. La rapie gazeuse offre les me mes avantages que les cryothe ances methodes plus traditionnelles avec cependant moins de se dapplication et des seances de plus courte duree ; cependant, cessite une formation spe cique pour une cette technique ne ` application securisee et le systeme (ainsi que les bouteilles de ` s facile a ` teux. La poche de gel traditionnelle est tre gaz) est cou me pour les patients, et elle nest pas che ` re ; utiliser, me , souvent limite e, re duit la surface de cependant, sa exibilite ` contact avec la peau. Le Cryocuff1 est vraiment simple a rapie et compression [3] ; ce syste ` me manipuler et allie cryothe te conc ciquement pour sadapter parfaitement a ` la a e u spe rature stable pendant une peau et permet de maintenir une tempe riode plus longue quavec la poche de gel. Le Cryocuff1 est pe cependant plus cher quune poche de glace et lutilisation e de la pompe AutoChill1 (qui fournit un froid continu combine e) ne cessite une alimentation e lectrique. et une pression pulse tude comporte quelques limites. Les re sultats se Notre e basent sur une analyse per-protocole et la randomisation de chantillon en trois groupes diminue le pouvoir statistique notre e tude. La cryothe rapie gazeuse hyperbare, le de cette e e xe e avec Cryocuff1, ainsi que la poche de gel congele sive ont provoque une compression associe e qui une bande adhe sultats de manie ` re positive ; les re sultats a pu inuencer les re

tudes comparant lassociation froid-compression a ` lune des e es isole ment restent conde ces deux composantes utilise s [5,6,16]. Par ailleurs, dans les groupes CC et CG, le troverse te utilise s le weekend Cryocuff1 et le CryotronTM nont pas e me traitement que le groupe CP) ; (les patients recevaient le me thodologie de notre e tude ree ` te les pratiques bien que la me pital (le weekend, seules les inrmie ` res cliniques de notre ho soccupent des patients), cette pratique a pu engendrer une ne ces de la cryothe rapie gazeuse par sous-estimation des be ` lapplication de la poche de gel. rapport a volution des Notre protocole na pas permis dexaminer le sultats e tant base s uniquement variables au l des jours, nos re valuation a ` J + 7 ; les mesures de lintensite de la douleur sur le ` J + 1 auraient e te utiles pour interpre ter les modications de a rapie sur la cette variable. Bien que limpact positif de la cryothe e dhospitalisation ait e te rapporte dans dautres e tudes dure ` tre. En effet, [21,38], nous navons pas pris en compte ce parame pend de plusieurs facteurs, tels que le futur la sortie du patient de lieu de vie (hospitalisation dans un service de revalidation, hospitalisation de jour ou retour au domicile du patient), la a ` linde pendance fonctionnelle (transferts, de placecapacite ou pas, pre sence ment) et la situation familiale du patient (isole ` domicile) [11,21]. dune aide a 2.6. Conclusion rence na e te observe e entre les groupes en ce Aucune diffe tudes sur un qui concerne les variables cliniques. Dautres e chantillon plus large, avec une application plus fre quente de la e rapie gazeuse et une pulve risation plus proche, sont cryothe cessaires an de conrmer que cette technique nest pas plus ne ` s une chirurgie de prothe ` se totale du genou que des efcace apre s traditionnelles dapplication du froid. modalite re ts claration dinte De clarent navoir aucun inte re t personnel ou Les auteurs de tude. professionnel pouvant inuencer les resultats de cette e TM Une societe a prete lappareil Cryotron pour un temps limite tude. et fourni plusieurs bouteilles de gaz an de mener cette e Remerciements ` remercier Mme Annie Depaifve, Les auteurs tiennent a ` res, M. Se bastien Wolfs ainsi M. Paul Remont, M. Richard Fre Tits pour leur aide pre cieuse et leurs conseils. que M. Andre References
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