Background and Evolution of Laser Lithotripsy

As urinary stone disease continues to increase in the United States and around the world, ureteroscopy (URS) with laser lithotripsy (LL) has become the most commonly used modality for stone treatment. More than 500,000 ureteroscopic stone cases are performed annually in the United States, based on extrapolation of data from the Urologic Diseases in America project. This increase in use of ureteroscopy is in part due to technological advances such as higher power laser systems, which have widely expanded the capabilities and efficiency of laser lithotripsy. Additional modes of laser lithotripsy, such as dusting and popcorning, can now be used in addition to traditional stone fragmentation to improve speed of treatment and better control stone particle size. However, these newer modes of laser lithotripsy are commonly applied at higher power and require increased irrigation to maintain a clear visual field. These laser and irrigation settings can substantially elevate fluid temperatures and intrarenal pressures, respectively.

Evidence of Complications from Elevated Temperature and Pressure

A number of in vitro studies, mathematical models and computer simulations have shown that laser energy applied at high power can elevate fluid temperature within the collecting system to dangerously high levels. The degree of temperature elevation is dependent on energy delivery (laser power, activation time and operator duty cycle) and the heat capacity of the system (fluid volume of calyx/ureter/collecting system, irrigation rate and irrigation temperature). Thermal tissue injury is dependent on both the degree of temperature elevation and the duration of exposure to elevated temperatures. This concept, developed by Sapareto and Dewey, is referred to as thermal dose and represents an accumulative measure of temperature during the treatment period. Cellular injury occurs when a thermal dose threshold of 120 to 240 equivalent minutes (based on tissue type) is exceeded. So proper prediction of the thermal tissue injury requires calculation of thermal dose and not simply measurement of temperature. Gross evidence of tissue injury has been demonstrated during in vivo porcine URS LL studies in our laboratory when thermal dose thresholds were exceeded.¹ Although there are limited human data, several studies have confirmed that significant temperature elevation can occur in the calyx and ureter during URS LL.^2,3 In a study examining laser activation in the ureter, 63% of patients experienced temperatures greater than 56C (exposure to 56C for 1 second will produce cell death).² Of this group of patients, 37% reported pain and/or had hydronephrosis on subsequent renal ultrasound concerning for ureteral stricture. While multiple factors can contribute to excessive heating, insufficient irrigation is perhaps the most important. However, what constitutes adequate irrigation has not been clearly defined. Laboratory studies have shown that temperature elevation can be well managed with room temperature irrigation delivered at 40 ml per minute for laser powers of 40 W applied continuously for 60 seconds.

High irrigation rates (see table) not only have been used to control intrarenal temperature, but also are necessary with advanced laser techniques, which produce dense clouds of stone fragments and debris that can obscure the endoscopic visual field. However, use of higher irrigation rate increases intrarenal pressure as measured during in vivo porcine studies (fig. 1). Pressures that exceed the threshold for pyelovenous backflow (30 mm Hg) increase the risk of tissue injury, fluid extravasation, systemic inflammatory response syndrome and sepsis. Ureteral access sheaths have been shown to reduce intrarenal pressure. This was confirmed in a recent human study that employed a wire pressure sensor during ureteroscopy.⁴ However, in a separate human study that also used wire pressure sensors, the pressure threshold for pyelovenous backflow was still dramatically exceeded in some cases, even with use of access sheaths.⁵ Furthermore, in many clinical circumstances, placement of an access sheath may not be possible or desirable.

Figure 1. In vivo porcine study of renal pelvic pressure during ureteroscopy (LithoVue ureteroscope) with irrigation applied at 0, 8, 15 and 40 ml per minute from peristaltic pump. 13Fr/15Fr access sheath was positioned with tip in proximal ureter.

Figure 2. Gross appearance of bivalved porcine kidneys demonstrating thermal injury. Left panel, inner blanched and outer hyperemic rings of tissue injury are observed after in vivo holmium laser activation within middle calyx at 40 W settings for 60 seconds with no irrigation. Dashed arc designates outer margin of hyperemic zone. Right panel, similar, but less pronounced, tissue effects in calyx at center after 60 seconds of laser activation at 40 W with 8 ml per minute irrigation.

Aside from the potential complications discussed above, we must also take a hard look at the current state of postoperative recovery following URS LL. While URS LL is commonly performed in the outpatient setting with patients discharged home after a typical 60-minute operative procedure, there is a stunning disconnect between the perceived minimally invasive nature of URS LL and the severity of postoperative pain, high postoperative emergency department visit rates (10% to 15%) and hospital readmission rates (5%). We must consider the possibility that elevated intrarenal temperature and pressure during URS LL produce tissue injury and inflammation (as seen with in vivo porcine studies), which in turn can lead to high postoperative pain, morbidity and readmission rates. Hence, one approach to decrease morbidity and improve the postoperative course for patients is to focus on better control and management of temperature and pressure during URS LL.

Current State and Future Directions

The introduction of high power lasers for lithotripsy occurred rapidly, without published evaluation of thermal or pressure risks. Currently, there is no guidance from industry, professional groups or regulatory bodies on selection of safe laser settings and irrigation rates. Recent bench and in vivo porcine data demonstrate that in certain circumstances clinical laser settings can induce dangerous temperature and pressure elevations and pathological injury (fig. 2). Although we perceive these events to be infrequent clinically, it is possible we are underestimating their prevalence. Thermal tissue changes may not be visually apparent at the time of URS LL. Although published human studies are limited at this point, they are not definitively reassuring. Proper investigation of thermal and pressure risks is needed in order to enhance and ensure the safety and tolerability of URS LL. The first step is to develop a collective clinical awareness that elevated thermal dose and intrarenal pressure can occur during URS LL. Research is needed to rigorously examine the extent of injury and inflammation that results from temperature and pressure insults, and assess the relationships with postsurgical symptoms and complications. This work can further inform development of new URS LL systems capable of real-time monitoring of temperature and pressure to enhance patient safety without limiting the capabilities and efficiencies derived from recent technological advances in laser lithotripsy.