Bone marrow edema in the knee in osteoarthrosis and association with total knee arthroplasty within a three-year follow-up

Objective The purpose of this study was to determine if a correlation exists between magnetic resonance imaging (MRI) findings of bone marrow edema (BME) in osteoarthrosis (OA) of the knee joint and need for total knee arthroplasty (TKA) within a follow-up period of 3 years.
Introduction
Osteoarthrosis (OA) is the most common cause of disability among the elderly population [1, 2]. OA is a condition where articular cartilage cannot maintain homeostasis in response to the forces acting on it. When homeostasis breaks down, there is a wide range of possible biologic responses based on the genetic background of the individual [3]. These responses may be anabolic or catabolic and involve cartilage, bone, and synovium. The exact pathogenesis of OA and the cause of the pain produced are unclear. OA is classically associated with degradation of the hyaline cartilage around the joint. However, cartilage contains no pain fibers. Other proposed sources of pain production in OA include periarticular structures and the underlying bone [3].
Several recent studies have examined bone marrow edema (BME) lesions and their association with OA [1, 4–10]. BME has been defined as an area of low signal intensity on T1-weighted images, associated with intermediate or high signal intensity findings on T2-weighted images. The literature suggests that there are two distinct types of BME. The first type occurs traumatically with injury to a joint and tends to resolve over a period of weeks to months [11–14]. This type of BME does not appear to have any long-term implications [15, 16]. The second type of BME occurs without trauma and may be associated with rapidly progressing osteoarthrosis. Zanetti et al. [9] suggest a possible link between atraumatic BME and increased pain in OA. Felson et al. [7] have suggested a possible link between BME lesions on magnetic resonance imaging (MRI) and progression of OA findings on MRI over time. Hunter et al. found that bone marrow lesions that enlarge with time are associated with more cartilage loss, compared with bone marrow lesions that stay the same size over time [17].
Despite the recent literature on BME, the implication of these findings on MRI and how they relate to clinical outcomes is unknown. Most studies have used the subjective complaint of pain as the only clinical correlate. There has been no measure of an objective clinical outcome related to the finding of BME. The purpose of this study was to determine if a correlation exists between MRI findings of BME of the knee joint and the incidence of total knee arthroplasty (TKA) within a follow-up period of 3 years.
Materials and methods
The entire database of knee MRI studies from 1995–1997 (over 4,000 studies) conducted at a large urban hospital system was used to select individuals with knee osteoarthrosis (OA). The study was reviewed and approved by the hospital’s institutional review board. An initial random search was conducted within this database to identify two distinct groups of patients. The first group had MRI reports containing the phrase “knee osteoarthrosis/osteoarthritis,” and the second group consisted of those containing the phrases “knee osteoarthrosis/osteoarthritis” and “bone edema.” The search for “osteoarthrosis/osteoarthritis” yielded 235 cases for review. The search for “osteoarthrosis/osteoarthritis” and “bone edema” yielded 146 cases for review. After these two initial groups were identified, a chart review was conducted on all 381 patients to identify and include only those patients who had at least a 3-year clinical follow-up appointment from the time of the MRI study. Subjects were also excluded if the reason for referral to MRI was post-traumatic or post-surgical. An initial review of the images was completed by an experienced musculoskeletal radiologist to exclude any subjects with evidence of recent post-surgical or post-traumatic changes not mentioned in the report. After this chart review and initial radiology review process, there were 38 patients in the OA-only group and 35 in the OA with BME group.
The same musculoskeletal radiologist who provided the initial review was blinded to the original interpretation of the MRI studies and the patient outcome, and reviewed all 73 studies. The radiologist was aware of the study hypothesis at the time of interpretation. The radiologist assessed each knee for the presence or absence of BME and assigned each subject into either the BME group or the no-BME group for further evaluation. After this review of the images, there were a total of 25 patients with OA only and 48 with OA and BME.
The OA-only group consisted of four males and 21 females, with an age range of 28–75 years, and an average age of 49.3 years. Conventional radiographs consisting of anteroposterior, lateral and sunrise views were available for review with 13 of the 25 patients, 52% of the group.
The OA and BME group consisted of 23 men and 25 women, with an age range of 35–82 years and an average age of 53.5 years. Conventional radiographs, again consisting of anteroposterior, lateral, and sunrise views, were available for review with 33 of the 48 patients, 68.75% of the group.
The conventional radiographs, when available, were reviewed by the musculoskeletal radiologist. Radiographic evidence of OA on the radiographs was assessed using the Kellgren–Lawrence scale [18] as follows:
NoneDoubtfulMinimalModerateSevere
According to this scale, evidence of OA includes (1) formation of osteophytes on joint margins or on the tibial spine, (2) periarticular ossicles, (3) narrowing of joint cartilage associated with sclerosis of the subchondral bone, (4) small pseudocystic areas with sclerotic walls situated usually in the subchondral bone, and (5) altered shape of the bone ends [18].
All patients had dedicated knee MR scans either on a GE 1.5-T magnet (23 in the OA-only group or 92% and 42 subjects in the OA with edema group or 87.5%) or a 1.0-T magnet (8% of the OA-only group, two subjects, and 12.5% of the OA with edema group, six patients).
MRI films were reviewed and interpreted by the musculoskeletal radiologist for all patients in the study. For each patient, the sagittal proton density sequences (TR range, 2,666–4,100; TE range, 14–33; 44 conventional spin echo studies [ET = 0], 29 fast spin echo studies [ET = 4–8], 3- to 5-mm section thickness, 16 × 16–18 × 18 field of view [FOV], 256 × 128–256 image matrix, bandwidth range 16–32), coronal proton density sequences (TR range, 2,316–3,950; TE range, 14–33; 44 conventional spin echo studies [ET = 0]; 29 fast spin echo studies[ET = 4–8]; 3-mm section thickness; 16 × 16–18 × 18 FOV; 256 × 128–256 image matrix; bandwidth range, 16–32), and coronal fat suppressed T2-weighted images (TR range, 2,400–3,200; TE range, 56–80; 3- to 5-mm section thickness; 16 × 16–18 × 18 FOV; 256 × 128–256 image matrix; bandwidth range, 15.6–16) were reviewed. Axial fat suppressed T2-weighted images (TR range, 3,000–3,600; TE range, 56–76; 1.5- to 10-mm section thickness; 16 × 16–20 × 20 FOV; 256 × 128–256; bandwidth range, 15.6–16) were available and reviewed for 69 of the 73 knees. For the four subjects who had no axial T2 imaging available, BME in the patellofemoral joint was not assessed.
The medial, lateral, and patello-femoral compartments of the knee joint were assessed. Evidence of OA on MRI was assessed using a modified Noyes arthroscopic classification [19] as follows:
NormalInternal changes only1–49% loss of articular cartilage50–99% loss of articular cartilage100% loss of cartilage with subchondral cortex intact100% loss of cartilage with ulcerated subchondral cortex
The most severe grade cartilage lesion within a compartment was utilized for the grading of that compartment. Also, the highest grade cartilage lesion on either side (femoral or tibial) of a compartment was used.
The radiologist then assessed each knee MRI for the presence or absence of BME. BME was defined as an area of intermediate or high-signal intensity findings on T2-weighted images. All patients in the BME group were then further classified into three separate, groups based on patterns of BME. Type I was termed “focal” and contained a small area of edema adjacent to a cartilage defect (Figs. 1 and 2). Type II was termed “global” pattern with marrow edema occupying most or all of a femoral or tibial condyle (Figs. 3, 4, and 5), and type III was termed “cystic” and was associated with a subchondral geode with a small area of BME (Fig. 6). The worst area of edema in a compartment was used in the classification. The presence or absence of meniscal tear was also noted.
Fig. 1Focal edema with a total knee joint replacement in a 51-year-old female patient. The radiograph demonstrated moderate loss of cartilage joint space medially and spurring of the tibial spines. Coronal fast fat suppressed T2-weighted image (TR 3000/TE 76/256 × 192) shows the loss of hyaline cartilage and a small focal area of edema in the medial aspect of the medial femoral condyle (arrow)Fig. 2Focal edema, no total knee joint replacement, in a 58-year-old male patient. Coronal fast fat suppressed T2-weighted image (TR 3000/TE 56/256 × 192) shows extrusion of the medial meniscus (curved arrow) and small adjacent areas of focal marrow edema (straight arrows). The medial meniscus has a degenerative horizontal cleavage tear approximating the tibial surface. Note also the moderate loss of hyaline cartilageFig. 3Global edema with a total knee joint replacement in a 65-year-old male patient. The radiograph demonstrated absence of joint space in the medial and lateral compartments, and irregularity of the subchondral bone plate of the lateral femoral condyle. Coronal fast fat-suppressed T2-weighted image (TR 3000/TE 72/256 × 192) through the knee shows extensive edema in the lateral femoral and tibial condyles, extending into the metaphyses (straight arrows). Note also the small extruded body of the degenerative and torn lateral meniscus (curved arrow)Fig. 4Global edema with a total knee joint replacement in a 72-year-old male patient. The radiograph demonstrated loss of cartilage joint space within the lateral compartment. Coronal fast fat-suppressed T2-weighted image (TR 3200/TE 72/256 × 192) shows extensive edema in the femoral and tibial condyles (arrows)Fig. 5Global edema, no total knee joint replacement, in a 58-year-old male patient. Coronal fast fat suppressed T2-weighted image (TR 3000/TE 76/256 × 256) through the knee shows extensive edema in the lateral tibial condyle and edema in some of the lateral femoral condyle (arrows). Note also the almost complete absence of hyaline cartilageFig. 6Cystic pattern with a total knee joint replacement in an 82-year-old female patient. The radiograph demonstrated subchondral lucency consistent with a geode and irregularity of the adjacent subchondral bone plate. Coronal fast fat-suppressed T2-weighted image (TR 3000/TE 56/256 × 192) shows complete loss of hyaline cartilage on the medial femoral condyle and adjacent moderate subchondral cystic areas consistent with geodes, and the adjacent bone marrow edema (arrows). Note also the extruded body of the medial meniscus containing a degenerative horizontal cleavage tear (curved arrow)
Generalized estimating equations (GEE) were used to determine which factors were related to receiving a TKA. There were eight subjects who had bilateral knee MRIs. GEE takes into account the correlation within an individual who had both knees involved, whereas a general linear model assumes that all observations are independent and does not allow for multiple observations from one individual. A multivariable logistic regression model using generalized estimation was also used to adjust for the age of the patients and to determine if the results were still significant after accounting for the age differences.
Results
There were 65 subjects in this study, with a total of 73 knees. After the final classification by the radiologist, there were 48 knees in the group with BME. There were a total of 15 knees or 31.125% in this group that had a TKA. There were 34 knees with a focal pattern of BME, 12 with a global pattern, and two with a cystic pattern. Of those with a focal pattern, 20.5% [7] had a TKA (Fig. 1). For those with a global pattern, 58.3% [7] had a TKA (Figs. 3 and 4), and for those with a cystic pattern, 50% [1] had a TKA (Fig. 6). These results are detailed in Table 1.
Table 1Patterns of edema and percentage of those who subsequently received TKAPattern of edemaTotal numberNumber with TKAPercentage with TKA (%)Focal34720.5Global12758.3Cyst2150All patterns of edema481531.2None2528
There were 25 knees in the group with no BME. There were a total of two knees or 8% of those without BME who had a TKA (Fig. 7; see Table 1).
Fig. 7No bone marrow edema with a total joint replacement in a 66-year-old female patient. Coronal fast fat-suppressed T2-weighted image (TR 2500/TE 80/256 × 256) shows almost complete loss of hyaline cartilage in the medial compartment and an extruded, degenerative torn medial meniscus. Note the absence of marrow edema
For statistical purposes, secondary to the small numbers of subjects in each subgroup, subjects were classified using the modified Noyes scale (0, 1, 2a, 2b, 3a, and 3b), and the data was grouped as cartilage damage less than 50% (0, 1, 2a) and cartilage damage greater than or equal to 50% (2b, 3a, 3b). For all three compartments of the knee, there were no statistical differences in rates of TKA between the groups that had less than 50% damage and the groups that had greater than 50% damage (see Table 2).
Table 2Cartilage loss seen on MR, as graded by the modified Noyes scale, and its relationship to the occurrence of TKAVariableNo TKAYes TKAOR95% CIp ValueMedial cartilage loss <50%17 (30%)2 (12%)2.770.71–10.720.14Medial cartilage loss ≥50%39 (70%)15 (88%)Lateral cartilage loss <50%42 (75%)10 (59%)2.060.74–5.700.16Lateral cartilage loss ≥50%14 (25%)7 (41%)PF cartilage loss <50%15 (28%)3 (19%)1.680.45–6.290.44PF cartilage loss ≥50%38 (72%)13 (81%)
For statistical analysis of the radiographs using the Kellgren–Lawrence scale, subjects who had scores of 0–2 (none, doubtful, or minimal) were compared with subjects who had a score of 3–4 (moderate, severe) to assess for statistical difference in the occurrence rate of TKA. Those subjects who had a Kellgren–Lawrence score of 3–4 were no more likely to have a TKA performed than those who had a score of 0–2 (see Table 3).
Table 3Radiographic findings, as graded by the Kellgren–Lawrence scale, and their relationship to occurrence of TKAScoreNo knee replacement(N = 35)Knee replacement(N = 11)OR95% CIp Value0–28 (23%)1 (9%)1.00060.9996–1.00160.233–427 (77%)10 (91%)
Table 4 shows the results of the subjects with BME, using the patterns of edema, compared to those without BME. Subjects who had BME of any pattern type were 5.48 times as likely to have a TKA when compared to subjects with no BME (p = 0.05). Upon further investigation, subjects with a global pattern of BME were 7.63 times as likely to have a TKA compared to subjects with focal, cyst, or no BME (p = 0.004). Subjects with global BME were 15.21 times as likely to get a TKA when compared to subjects without BME (p < 0.001).
Table 4Comparison of bone marrow edema patterns and their relationship to occurrence of TKAVariableNo TKAYes TKAOR95% CIp ValueNo BME23 (41%)2 (12%)5.480.98–30.680.05BME of any pattern33 (59%)15 (88%)Global BME5 (9%)7 (41%)7.631.89–28.340.004All other patterns (focal, cyst, none)51 (91%)10 (59%)Global BME5 (18%)7 (78%)15.212.38–97.10<0.001No BME23 (82%)2 (22%)First, no bone marrow edema is compared with BME of any pattern. Next global BME is compared to all other patterns, including no edema. Finally, global BME is compared with no BME.
Table 5 demonstrates the results of a univariate comparison between subjects with BME and without BME, and their scores on the modified Noyes and the Kellgren–Lawrence classifications. For the medial compartment only, subjects who had high scores on the Noyes and Kellgren–Lawrence scales tended to have BME, whereas those subjects with lower scores on the Noyes and Kellgren–Lawrence scales tended to have no BME.
Table 5Univariate comparisons between those knees with BME and those without BME (t tests)VariableScoreNo BMEBMEp ValueModified Noyes score lateral compartment0–2a20 (80%)32 (67%)0.2322b–3b5 (20%)16 (33%)Modified Noyes score medial compartment0–2a11 (44%)8 (17%)0.0122b–3b14 (56%)40 (83%)Modified Noyes score patellofemoral compartment0–2a4 (17%)14 (31%)0.1932b–3b20 (83%)31 (69%)Kellgren–Lawrence score lateral compartment0–213 (100%)26 (79%)0.0713–40 (0%)7 (21%)Kellgren–Lawrence score medial compartment0–29 (69%)11 (33%)0.0273–44 (31%)22 (67%)Kellgren–Lawrence score patellofemoral compartment0–25 (42%)11 (33%)0.6063–47 (58%)22 (67%)
The presence of a meniscal tear did not correlate with subsequent TKA. There was no significant difference in the gender between the group that received a TKA and those that did not. The group of subjects who had a TKA were 12.6 years older than those who did not have a TKA (p = <0.001). In this study, the odds of having a TKA increase by about 1.11 times for each year increase in age.
A multivariable logistic regression model using generalized estimation was performed to account for the age difference in the groups and assess whether or not the results were still significant despite the age difference. Table 6 displays these results and demonstrates that, after accounting for the age difference, subjects who had BME of any pattern type were 8.95 times as likely to have a TKA when compared to subjects with no BME (p = 0.016). Subjects with global BME were 13.04 times as likely to get a TKA when compared to subjects without BME (p < 0.01). Subjects with a global pattern of BME were 5.45 times as likely to have a TKA compared to subjects with focal, cyst, or no BME (p < 0.05).
Table 6Results of the multivariable logistic regression model using generalized estimation to account for the age difference in the groups that received a TKA versus those that did not Outcome: TKAVariableOR95% CIp-valueModel 1BME versus no BMEf8.951.49–53.680.0164Age1.131.07–1.20<0.0001Model 2Global BME versus No BME13.042.06–82.580.0064Age1.060.99–1.150.11Model 3Global BME versus all other patterns (focal, cyst, and no edema)5.451.02–28.960.0467Age1.1071.05–1.170.0002
Discussion
BME has previously been noted in the musculoskeletal system in osteoarthrosis and other conditions [1, 4–11, 13, 14, 20]. Felson and colleagues have examined BME and its relation to progression of knee osteoarthrosis and noted that BME is a potent risk factor for structural deterioration in knee osteoarthrosis [1, 7, 17]. Its relation to progression is explained in part by its association with limb alignment. In two of his studies, medial bone marrow lesions were seen mostly in patients with varus limbs and lateral lesions were seen mostly in those with valgus limbs [7, 17].
Link and colleagues [4] reviewed MR findings in osteoarthrosis and noted that cartilage lesions, BME patterns, and meniscal and ligamentous lesions were frequently demonstrated as MR changes in patients with advanced osteoarthrosis. However, in this study, there was no significant correlation between MR and clinical findings.
A recent study conducted by Kornaat et al. [21] examined multiple imaging findings and their association with clinical symptoms. Their results suggest that only findings of a large-joint effusion or the presence of an osteophyte in the patellofemoral compartment were associated with pain and/or stiffness. They found no association between BME and symptoms of pain or stiffness.
Three studies have reviewed the MR appearances with histopathology findings [6, 9, 10]. Bergman and colleagues in their study found that subchondral bone marrow changes were present in seven of nine patients undergoing total knee replacement [10]. Histopathologically, those regions showed focal areas where fibrous tissue replaced fatty marrow in the subchondral trabecular space. Zanetti and colleagues reviewed the histopathological findings in 16 patients who had MR before total knee replacement. The BME pattern consisted of normal tissue and a smaller proportion of several abnormalities including bone marrow necrosis, bone marrow fibrosis, abnormal trabeculae, BME, and bone marrow bleeding. They concluded that a BME pattern in knees with osteoarthrosis represents a number of non-characteristic histological abnormalities [9].
Nolte–Ernstein and colleagues examined the correlation between MR and histological findings of degenerative bone marrow lesions in experimental osteoartrhosis models in canine knee joints [6]. In these experimental lesions, the histopathology revealed 21 osteosclerotic lesions and 5 intraosseous cysts. Histopathological findings showed different degrees of osteosclerosis associated with bone marrow degeneration. Cystic lesions were of two types: subchondral epiphyseal cysts and synovial cysts within a large tibial osteophyte. High signal intensity on T2-weighted images and decreased signal intensity on T1-weighted images indicated high fluid content.
None of these prior studies specifically looked at the BME pattern on MR. Our classification of the patterns into global, focal, cystic, and absence of edema is an attempt to subdivide the presence or absence of edema in osteoarthrosis. However, this attempt is limited by the absence of histopathological findings.
We were surprised by the significantly increased risk of knee joint replacement with the global pattern of BME in relation to the other patterns. It appears that the more extensive and intense the BME, the more likely it is for the patient to have symptoms. The global pattern of BME was the best predictor of risk of TKA within 3 years, as those subjects with the global pattern were over five times as likely to receive a TKA when compared to those with any of the other patterns and over 13 times as likely to have a TKA when compared with subjects with no BME, after accounting for the age difference.
We were also surprised by the lack of association between cartilage loss and the likelihood of total knee replacement. Intuitively, one would think that the greater the cartilage loss, the more likely the possibility of total knee replacement. However, Link and colleagues [4] noted that clinical findings showed no significant correlation with the extent of cartilage loss on MR imaging. In this study, the lowest scores for pain and function loss were found in patients without cartilage lesions. However, the highest scores for pain, stiffness, and function loss were found in patients with less than 50% cartilage loss. The lowest scores for stiffness were found in patients with more than 50% cartilage loss and full-thickness lesions. These findings further support the theory that cartilage loss may not be the primary source of pain in patients with OA of the knee.
We did find, in the medial compartment only, that subjects with high grades of cartilage loss or advanced degenerative changes on radiographs tended to have some degree of BME. The lack of association between cartilage loss and the likelihood of TKA in our study could be a reflection of the limitations of the Noyes classification system. However, other investigators have also found that radiographic signs of cartilage loss may not relate to the degree of clinical symptoms. As mentioned above, Link and colleagues found no correlation with the extent of cartilage loss on MR and clinical findings. In their study, they also used a modified Noyes classification system [4]. Kornaat et al. also found no correlation between the extent of cartilage damage seen on MR imaging and clinical symptoms of pain and stiffness. They used a grading scale based on the maximum diameter of cartilage defects and the depth of the lesion based on the percentage of cartilage loss [21].
In clinical practice, OA is associated with the radiographic findings of joint space loss and subchondral sclerosis, presumably secondary to cartilage loss that results in pain. However, as stated earlier, there are no pain fibers in hyaline cartilage [3]. Furthermore, many patients have pain out of proportion to their radiographic findings. Our study may provide an insight into another possible mechanism for pain production in OA of the knee. While not every patient with OA warrants an MR scan, those patients without the classic presentation may benefit.
We did find that patients who had a TKA were 12.6 years older than those who did not have a TKA. Patients who are older are more likely to have OA and, in particular, more severe OA. Surgical replacement of the knee is more likely to occur in an older patient with OA than a younger patient with the same severity of OA. After further statistical analysis, we however found that our BME results were still significant despite the differences in age.
This paper has several limitations. Most patients who have a TKA do not get a pre-operative MR, and therefore, we may be dealing with a pre-selected population. What we have called “BME” on MR may not be true edema but may relate to other histologic findings as noted earlier. Our numbers are also small, and we had to group some of our subsets together for statistical analysis. Only one musculoskeletal radiologist was involved in the review of the radiology. There was also no arthroscopic correlation for cartilage defects or presence of meniscal tears. Our study is limited by the fact that it is retrospective. To generate a group of MR scans to review, we had to use a keyword search to identify potential subjects. We would have obviously missed all scans where the specific terminology “bone edema” or knee “osteoarthrosis/osteoarthritis” was not utilized. However, we feel that this is a relatively minor limitation, as we were able to generate 381 cases for review. Another potential limitation in the retrospective study design is the possibility of missing subjects who received follow-up at a different institution or those whose symptoms resolved without treatment.
In summary, we reviewed a series of knees in patients with osteoarthrosis and evaluated the pattern of BME, cartilage loss, radiographic findings when available, and the incidence of total knee joint replacement within a 3-year follow-up. Subjects with any bone marrow edema pattern were more likely to have a total knee joint replacement compared to subjects with no bone marrow edema. The worst prognostic pattern was the global pattern of bone marrow edema. Subjects who had a total knee replacement were also older than those who did not. However, even allowing for age, the global pattern of BME remained the variable with the highest statistically significant association with the incidence of total knee replacement.

bone marrow edema
osteoarthrosis
total knee arthroplasty


Handheld computers in critical care

Background Computing technology has the potential to improve health care management but is often underutilized. Handheld computers are versatile and relatively inexpensive, bringing the benefits of computers to the bedside. We evaluated the role of this technology for managing patient data and accessing medical reference information, in an academic intensive-care unit (ICU).
Introduction
The rapid development of computing technology has had a major impact on health care, particularly in technology-oriented areas such as critical care. Electronic patient records require a major commitment by the institution, in hardware, software, training, and support. In many places, bedside care of patients still relies on paper records or nonintegrated computer systems that do not take full advantage of their data-management capabilities [1]. Even where there are advanced computerized systems, the bedside clinician may still rely on written notes for patient management and billing, and refer to pocket textbooks or printed management algorithms.
For busy clinicians, the use of computers for hospital-based clinical care may be hampered by the computers' inaccessibility. Handheld computing technology is versatile and relatively inexpensive [2], combining many of the benefits of electronic patient records and paper charts. Handheld computers have been described in various medical situations; early reports describe programmable calculators used to make complex calculations in intensive-care units (ICUs) [3]. Handheld devices are increasingly being used by physicians for a variety of functions, such as scheduling, accessing drug reference information, patient data storage and billing. However, there are few published reports describing the benefits of this technology [4, 5, 6, 7].
In view of the potential advantages and increasing use of handheld computers in medicine, we evaluated the benefits and drawbacks associated with introducing this technology in an academic ICU.
Materials and methods
Hardware
The Palm III series handheld device (Palm device, Palm Canada Inc, Toronto, Ontario) was used, as some of our staff were familiar with this equipment. It is a pocket-sized (8 × 12 cm; 165 g) computer with a 4-Mb (PalmIIIx) or 8-Mb (PalmIIIxe) memory. It has an infrared data association (IrDA) port that allows transmission of data between Palm devices and other IrDA-compatible devices such as printers, laptop computers and cellphones. The device has a monochrome 160 × 160 pixel liquid-crystal display screen (Fig. 1) and allows the user to input data either by writing on the touch-sensitive screen with a stylus or by tapping on an on-screen keyboard. Handwriting is deciphered by Graffiti handwriting-recognition software (Palm Inc, Santa Clara, CA, USA), which requires the user to learn specific characters. For users who preferred to enter data using a keyboard, two GoType keyboards (LandWare Inc, Oradell, NJ, USA) were found in the ICU. When the Palm device was placed in this keyboard, the user could type in the standard way.
Software
Each personal digital assistant (PDA) was installed with medical reference information as well as hospital and ICU specific guidelines (Table 1). This occupied approximately 2 Mb of memory. The applications that come with the PDA (Addressbook, Datebook, Memopad, To Do list) were used for essential telephone numbers as well as call and teaching schedules, but additional software was required for medical databases. The spreadsheet database program JFile (Land-J Technologies, Orlando, FL, USA) was used for reference information, such as drug doses and laboratory reference ranges. The text readers AvantGo (AvantGo Inc, San Mateo, CA, USA) and iSilo (www.isilo.com), which convert word-processing and HTML documents, were used for textual medical reference information. CbasPad, a Tiny BASIC programming language interpreter and editor, was used to develop software to perform common critical-care calculations, such as calculated creatinine clearance and intravenous infusion rates. Additional software for medical reference data was introduced during the study period, including ePocrates qRx [8], a drug information database.
Patient data were entered into the Memopad using a customized template generated with MemoPlus (Hands High Software Inc, Palo Alto, CA, USA). The information entered included demographic data, medical history, current diagnoses, therapy, procedures performed, and management plan. Data was transferred between medical personnel using the PDA's infrared beaming ability. As hospital policy requires a paper record, daily notes were generated by Palmprint software (Stevens Creek Software, Cupertino, CA, USA) using infrared transmission to an HP Laserjet 6P printer (Hewlett Packard, Palo Alto, CA, USA). Various software packages for patient data management (shareware or commercially available software) were evaluated during the study period.
In the light of focus-group feedback, a more comprehensive reference database was developed. The electronic files for the Critical Care Handbook of the Massachusetts General Hospital [9] were provided by the publishers, and converted to a PDA-readable (iSilo) format. This 1.4-Mb file contained the full text of the book, with multiple hyperlinks, and some of the images. Hard copies of the book were also obtained.
Study subjects
PDAs were given to the ICU attending physicians, the rotating resident trainees, and other medical staff. Four to six residents (postgraduate years 2 to 4) worked in the ICU at any one time. On the first day of their ICU rotation, residents were taught how to use the PDA in a 1-hour seminar. The principle investigator and research team were available for further help and troubleshooting throughout the study The research team was responsible for installing and updating software and schedules. Patient data was entered by residents, either during morning rounds or when patients were admitted to the ICU. The updated database was beamed to the on-call resident in the evening and transmitted back to the team in the morning, with new admissions added.
Methodology
An independent evaluation company (Smaller World Communications, Richmond Hill, Ontario) with experience in focus-group methodology was contracted to develop the qualitative methodology, collect data through focus-group meetings, and analyze the data [10, 11]. A preliminary moderator's guide was developed and tested on an expert panel, comprising two critical care physicians, an anaesthesiologist, three medical residents with experience in data management or PDAs, and a representative from Palm Canada Inc. The moderator's guide was designed to stimulate discussion about users' familiarity with the technology, the benefits to patient management, and the drawbacks encountered. Finally, ideas were generated for new applications for the technology and improvements to the hardware and software. Three focus groups were held with the residents and staff who used PDAs in the ICU. Tapes were transcribed verbatim and the notes were analyzed for themes by a research analyst [12]. Interim reports from the meetings were provided to the investigators. On the basis of this feedback, ongoing improvements were made to the medical databases and patient-management software.
The PDA reference database was evaluated objectively using a crossover study. The trainees' rotation was split into two 3-week periods. One of the periods was allocated as a control (PDA-free) block and in the other the PDA was available. Two groups of trainees were studied: in one the PDA period preceded the PDA-free period, and in the other, the order was reversed. During the PDA period, trainees had access to the full PDA database as well as the electronic version of the Critical Care Handbook of the Massachusetts General Hospital [9]. The printed copy of the handbook was given to trainees during the PDA-free period.
Objective evaluation was accomplished using a pair of standardized clinical scenario tests made up of 20 questions answered over 30 minutes. The questions were about common critical-care problems, drawn randomly from a pool of questions written by physicians in our ICU and at other teaching hospitals in the Toronto area. Trainees made use of the textbook (control period) or PDA database (study period) during the examination. To standardize for the possible difference in difficulty between the two tests, 11 General Internal Medicine trainees, not involved in the PDA study, wrote both the tests. This generated a mean and standard deviation for each test. Study trainees' results were expressed as the standard deviation above or below this control mean, and compared using a permutation test, with P < 0.05 considered significant.
Results
During the 6-month study period, PDAs were used by 20 physicians (4 attending physicians, 1 research fellow, and 15 rotating medical residents) and 6 paramedical staff (3 respiratory therapists, 2 pharmacists, and 1 nurse educator). The three focus groups had a total of 19 participants. Two residents who were unable to attend participated in telephone interviews. Each focus group had six or seven participants, a number within the recommended range [11]. Only five of the users (19%) had previous experience with the PDA computing format.
Physical attributes
Users found the PDA to be a convenient pocket size, allowing it to be available at all times. The screen was clear and easy to read, although not ideal for long text documents or large tables. Many users became proficient in text entry using Graffiti, while others preferred to use the GoType keyboards. Of the 19 PDA units used during the 6-month study period, only one had a technical malfunction requiring replacement. Two were damaged after being dropped and needed to have their screens replaced. No other problems were encountered.
Medical reference databases
Reference databases used regularly by medical residents included the critical-care drug dosing reference, ventilator weaning protocol, and electrolyte correction application. The calculation programs (creatinine clearance, ideal body weight) were found to be useful by the pharmacist and some residents. The ventilator weaning protocol was used by medical staff, as well as respiratory therapists, allowing regular assessment of whether patients met the criteria for extubation.
Many databases were, however, not fully used. This appeared to relate more to inadequate training than to faults in the databases. In many cases, the PDA users were unaware that certain information was in their PDAs. This was because data were located on separate software programs (J-file, AvantGo, Cbas, Memopad) and may have been difficult to find. The PDA had a global 'Find' function to search for keywords, but this does not incorporate some of the added software programs, such as AvantGo. A unified database program with a search capability was suggested as a useful addition.
Patient-management software
Patient information was managed using the text-based MemoPlus software and a customized template. This required text entry on the PDA. Several modifications to the template were made during the study period. Residents responsible for patient data entry described difficulty entering data for new patients and keeping patient information updated during busy weekends. Attending staff found the patient data useful, particularly when they were taking over care of patients at the beginning of their on-call duties. Transferring the care of critically ill patients to a new physician is time-consuming and potentially stressful. The PDA patient database improved the staff's knowledge of patients, especially of previous medical problems in patients with complex conditions who had had a long stay in hospital. It also gave staff access to patient information when they were out of the ICU, aiding decision-making. During ICU rounds, the summarized chronological information was useful to find out how long intravenous lines had been in place and to review antibiotic therapy. Less benefit was noted in short-term patients. During night call, the patient summaries were of value when residents were called to see patients with whom they were not very familiar.
In our ICU, a daily physician note is written in the patient record. The print function to create a daily note reduced duplication of work, but the process for entering patient data was found to be time-consuming initially. While residents did not feel that the patient-management application (MemoPlus) improved efficiency, it did increase their knowledge of the patients.
During the study period, other commercially available patient-management software systems were evaluated. These had the advantage of easy data input using single keystrokes for date entry and 'pop-up' lists of drugs and diagnoses. While this simplified data inputting, no system was found to be ideal for the ICU. Many of these systems did not support the infrared data transfer or printing functions.
Other uses of the software
Study participants used a variety of other applications on a regular basis. Having the call and teaching schedules easily accessible was considered a benefit. The telephone list of hospital numbers was found to be valuable and the To Do list was used by most users to keep track of their work. Teaching rounds and morbidity and mortality rounds were facilitated by using archived patient data. Many participants used the Memopad to take notes in teaching seminars.
Suggestions for change
The focus-group discussions generated a number of suggestions for improvement. The hardware unit was considered suitable, but a more robust one may be needed in view of the two damaged screens. Because most of the users had had no previous experience with the PDA, additional teaching sessions and follow-up training were suggested to make optimal use of the technology. This would have helped users to become more aware of the many databases available on their PDA. In this regard, the medical information on the PDA would clearly benefit from integration into a single, searchable program.
The patient-management software would be more user-friendly if the data could be entered with minimal effort, using customized pull-down lists of drugs, diagnoses, and procedures. The demographic data could be entered and updated daily by a ward clerk. Alarms were suggested - for example, to warn of prolonged intravenous line duration or the end of a course of antibiotic therapy. While transmission of data between staff by infrared was found to be useful, synchronization with the hospital electronic patient record was considered the optimal situation.
Objective evaluation
Two groups of four trainees took part in each crossover study. Half of the residents had prior experience with PDAs. No difference was noted in their subjective preference for the PDA or printed copy of the handbook, and the individual's preference did not correlate with previous PDA experience. Comparison of the test scores revealed no difference between the scores in the PDA-assisted test and the paper-assisted test, analyzed after correction for difficulty using the control mean and standard deviation.
Discussion
This study prospectively evaluated the benefits and drawbacks associated with the introduction of handheld computers in an academic-critical care environment.
Who benefitted most?
The introduction of handheld computers was well received by all users, despite differences in their familiarity with these devices. The most favourable response was from the more senior staff, namely, the attending physicians and fellows. This may be because of the longer time they were involved in the study, allowing more familiarity with the PDA platform. They were also more likely to benefit from having patient data available while on call outside the ICU. Furthermore, they were usually not responsible for entering patient data. Clearly, two conditions that might enhance the acceptance of these technological changes are adequate education and ease of data entry. Although an initial education session was held, it was when the junior medical staff in the study were beginning their rotation in an unfamiliar environment.
Making the devices more user-friendly
The patient data applications assessed were not ideal but did enable us to identify several criteria for a user-friendly system. These include ease of data entry using shortcuts and lists, limiting the range of data stored to that essential for patient management, and the ability to transmit data easily between staff. It is important that this computerized patient database should decrease workload and not cause duplication in work. In our study, enabling residents to print a daily note from their handheld computer offset the additional work of data entry. Ideally, the handheld system should be integrated with the hospital electronic patient record, allowing direct entry of demographic data as well as access to laboratory data.
A wireless capability may also have significant benefits with respect to medical information databases. This would allow access to Medline searches and evidence-based guidelines. While internet access is available from desktop computers in the ICU, the ability to perform these searches on rounds or while consulting outside the ICU may be beneficial.
Databases on paper or on screen?
The comparison of paper and electronic databases did not reveal an advantage of one medium over the other. No significance difference was observed between the objective scenario test scores using the PDA or the paper database. The fact that equivalent results were obtained using this single database may suggest a potential benefit of using the PDA. The memory capability of the 8-Mb device would allow the trainees to carry five reference texts each of a size similar to that of the Critical Care Handbook of the Massachusetts General Hospital.
What is needed
Critical-care decision-making requires rapid access to strategic clinical data as well as to medical reference information. A patient in an ICU generates a large amount of data, and the number of information variables may exceed what clinicians can integrate and process [13]. Current information technology has the potential to realize the needs of the intensivist, but no customized product has been developed for this use. Handheld technology has a definite role to play, but systems need to be developed specifically for the critical-care environment to optimize real-time patient data management and communication between health care workers.
Abbreviations
HTML = hypertext markup language; ICU = intensive-care unit; IrDA = infrared data association; Mb = megabytes; PDA = personal digital assistant.

computer communication networks
medical informatics
medical technology
microcomputers
point-of-care technology