Compared with manual control, automated systems increased the percentage of time a given variable was maintained in a desired range by 21.2% (95% CI, 11.5%−30.9%; I2 = 0.96, P = 0.001 as shown in Figure 4). In all studies, the length of time was longer in the automated control group. This difference reached statistical significance in 6 trials.22,29,32,43,44,46 All articles provided data corresponding to the secondary outcome of this review. In 3 articles,22,42,44 the authors found a statistically significant reduction of episodes of hypoglycemia in the automated group. In the remaining articles, even if not statistically significant, the number of episodes of hypoglycemia or hyperglycemia was higher in the control groups. Performing subgroup analyses, we observed that automated systems decreased the percentage of time of inadequate control (below or above the target range) of BG compared with the manual group by −6.5 % (95% CI, −11.3% to −1.8%, I2 = 0.92, P = 0.010; Figure 5).
Compared with manual control, automated systems increased the number of measurements that were within the target range (odds ratio, 1.44; 95% CI, 1.04–2.0; I2 = 0.77, P < 0.0001). The number of patients with 1 or more episodes of hypotension or hypertension was similar between the manual and automated group in 1 trial.34 In the other trial,49 the number of patients with hypotension was significantly higher in the manual group (P = 0.001).
In this systematic review and meta-analysis of randomized clinical trials, we evaluated the accuracy and safety of closed-loop systems compared with manual control. Automated systems increased the length of time that a given variable was maintained in the desired range compared with manual control. This difference reached statistical significance in the majority of trials (28 of 36). This likely suggests that automated systems can obtain a better control of depth of anesthesia, BG level, and ventilation. Because of the limited number of studies gathered, no conclusion could be drawn concerning automated systems for vasopressor administration and for insulin infusion in ICU patients. The incidence of overshooting or undershooting a given control target was reduced during automated control or was at least similar between the groups in all trials reporting this outcome (29 of 36).
To assess the clinical significance of the control aspect of closed-loop systems, we can deduct from this meta-analysis that there is a significant improvement in the percentage of time of “desired” control (parameter in the predefined range of target control). Interestingly, this improvement ranged from 12% for the maintenance of specific ventilation parameters (Figure 6), to 17% for maintenance of a target level of anesthesia (Figure 2) and to 21% of maintenance of a target level of BG level in patients with diabetes mellitus (Figure 4). As an example, for 1-hour duration of anesthesia, the targeted level of anesthesia would be maintained for 10 minutes longer than with manual control: these authors would regard this as a significant clinical advantage.
We chose undershooting or overshooting as a parameter of safety assessment: for example, we would consider undershooting a given BIS target as putting the patients at risk of either waking up or having periods of awareness. The improvement ranged from 7% for avoidance of overshooting or undershooting parameters of ventilation and avoidance of either hypoglycemia or hyperglycemia (Figure 5) to 12% for avoidance of undershooting or overshooting a given level of anesthesia. If one considers that undershooting a given level of anesthesia, too light a level of hypnosis, puts the patient at risk of awareness, whereas overshooting might be related to worse outcome, 5 to 6 minutes less time during 1 hour of anesthesia of exposure to these risks is a significant clinical improvement of closed-loop systems compared with manually administered anesthesia.
There are several limitations to our review. First, we decided to perform a review and meta-analysis focusing on the comparison between automated systems and manual control in different medical fields. As a consequence, we analyzed different kinds of closed-loop systems. We cannot draw any conclusion about the superiority of one technological system compared with another. A second limitation was the limited number of studies retrieved for automated insulin delivery in ICU patients and closed-loop systems for vasopressor administration. Third, the overwhelming majority of trials qualified for an intermediate quality score. Only 1 study49 reported a proper blinding procedure. Another limitation was the high heterogeneity of the studies. This marked heterogeneity can be explained by multiple factors. We included trials that investigated both pediatric and adult patients. Moreover, regarding closed loop for insulin administration, the desired target range for the BG concentration varied widely within the studies (as shown in Table 1). The high heterogeneity likely reflects the different durations of the observational period selected by the authors (eg, 36 hours,29 6 weeks44). The choice of comparing differently designed and engineered automated systems might have increased the heterogeneity.
Another limitation of the review is related to the type of studies published: no studies focused on the influence of closed-loop systems on patient outcome such as reduced length of stay, reduced morbidity, or mortality.
In summary, automated systems increased the length of time that a given variable was maintained in the desired range compared with manual control. The incidence of overshooting or undershooting a given control target was reduced during automated control or was at least similar between the groups in all trials reporting this outcome.
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