Effect of Pulse Energy,Frequency and Length on Holmium:Yttrium-Aluminum-Garnet Laser Fragmentation Efficiency in Non-Floating Artificial Urinary Calculi

Abstract

Background and Purpose:

Holmium:yttrium-aluminum-garnet (Ho:YAG) laser lithotripsy is the standard lithotrite in ureteroscopy. We investigated the influence of pulse frequency, energy and length on the fragmentation efficiency of Ho:YAG laser lithotripsy in non-floating artificial stones in vitro.

Materials and Methods:

Stone fragmentation efficiency of three different Ho:YAG laser devices were evaluated in vitro at different pulse energy (1.0 and 2.0 J) and frequency settings (5 and 10 Hz), resulting in a standardized output power of 10W, respectively. Where possible, pulse length was modified (350 vs 700 μsec). Each setting was performed with a 273 μm and a 365 μm fiber. Lithotripsy was conducted using non-repulsive stones consisting of soft stone (plaster of Paris) and hard stone composition (Fujirock type 4).

Results:

Our results showed an increased stone disintegration efficiency at higher pulse energy (2.0 J/5 Hz vs 1.0 J/10 Hz) independently of two fiber diameters and stone types applied in this study (P < 0.05 in 18 of 20 groups). Similarly, reduction of the pulse length from 700 to 350 μsec resulted in a higher stone disintegration (P < 0.05 in 13 of 16 groups). This effect was most prominent when applied to soft stones. Higher fiber diameter was not constantly associated with an increase in stone disintegration.

Conclusion:

We demonstrate that an increase of pulse energy and a reduction of pulse length at a standardized output power of 10W can improve Ho:YAG laser fragmentation efficiency in vitro in nonfloating stones. These results may potentially affect clinical practice of Ho:YAG laser lithotripsy in impacted or large stones, when retropulsion is excluded.

Introduction

T he surgical management of urinary stone disease has undergone a dramatic development over the past two decades. Advanced minimally invasive approaches have been successfully introduced into clinical routine. Retrograde ureteroscopy has become the first-line management option for ureteral and intrarenal stones in many centers because high success rates and low complication rates were reported, expanding its indications for large renal and bilateral stones, pediatric patients, and patients with continued oral anticoagulation.^1,2

Stone comminution can be achieved by a variety of devices. Holmium:yttrium-aluminum-garnet (Ho:YAG) laser lithotripsy is the preferred device in flexible ureteroscopy because a reliable disintegration of all types of stones can be achieved with low risk of uro-epithelial damage.^3
–5 Previous studies have indicated an effect of power settings, pulse length, fiber type and stone composition on the fragmentation efficiency and retropulsion in Ho:YAG laser lithotripsy.^6

–10 In the present study, we investigated whether variation of pulse energy, frequency and length at a standardized output power can optimize fragmentation efficiency in vitro using nonfloating phantom stones.

Materials and Methods

The long-pulsed Holmium:Yag laser devices Sphinx (Lisa Laser, Germany) and Odyssey 30 (Cook Medical, Ireland) were included because they allowed standardized settings of pulse energy, frequency and length. In addition, the Revolix Duo laser (Lisa Laser, Germany) was included in this study. This dual-mode device can operate in a 2 μm continuous-wave laser mode or in a 2.1 μm pulsed Ho:YAG laser mode, which was used in the present study. Each device was used at two different pulse energy rates (1.0 and 2.0 J) and frequency settings (5 and 10 Hz), all resulting in a standardized output power of 10W, respectively. Where possible (Sphinx and Odyssey 30), pulse length was modified between 350 vs 700 μsec both in the 1.0 J/10 Hz and 2.0 J/5 Hz setting. Pulse length of the Revolix Duo is not adjustable and was used at predefined pulse lengths of 170 μsec at 1.0 J and 280 μsec at 2.0 J. The Odyssey 30 was operated with bare-ended 273 μm and 365 μm OptiLite fibers (Cook Medical); the light of the Sphinx and the RevolixDuo laser was transmitted via bare-ended 273 μm (FlexiFib) and 365 μm fibers (PercuFib, both Lisa Laser).

Artificial stones with two different degrees of hardness were produced. Plaster of Paris was used to simulate a soft stone composition (concentration 4:3 (w/v in H₂O) in water; Quick-Mix, Germany), and Fujirock type 4 dental stone (concentration 10:3 (w/v in H₂O); GC Europe, Belgium) was used as a hard stone composition. A standardized volume of 20 mL of wet stone mix was poured in cone-shaped plastic molds to obtain stones of a defined size and shape with an even top and bottom surface. Stones with visible cracks or bubbles were excluded. Stones were oven-dried at 40°C for at least 72 hours before commencing the experiments.

All stones were incubated in water at 21°C for 30 minutes before lithotripsy until they had reached a constant weight. Lithotripsy experiments were performed in a water basin for 60 seconds (600 J per calculus and setting) on a surface area of 5 × 5 mm in contact mode (hand-assisted). Stones were fixed at their bottom to exclude retropulsion. After the experiments, stones were oven-dried at 40°C for 72 hours. Fine-grained sand was used to measure the volume of the craters on a scale exact to ± 0.0001 g. This method allows exact measurements and excludes a possible bias of weighing retained fluid within the stones. In rare cases, where larger pieces of the stone surface broke away, samples were excluded from the study.

Study design and statistical analysis

The primary endpoint of this study was measurement of the volume of the craters (mm³) induced by Ho:YAG laser lithotripsy to evaluate the fragmentation efficiency using varying settings of pulse energy, frequency, and length at a standardized output power of 10W. Secondary endpoints were differences in fragmentation efficiency with regard to a variable hardness of stones and variable fiber diameters of 273 μm and 365 μm.

As a first step, we compared the fragmentation efficiency at a standardized output power of 10W using variable adjustments of pulse energy and frequency (5 Hz/2.0 J vs 10 Hz/1.0 J) applied to two different stone compositions (plaster of Paris and Fujirock), respectively. As a second step, we investigated relative changes in stone fragmentation efficiency, switching the pulse length between 700 μsec and 350 μsec. All results were analyzed separately, forming two groups for the 365 μm and the 273 μm fiber.

Sample size was at least n = 10 for all settings using Fujirock stones and at least n = 6 for experiments using plaster of Paris phantom stones. Statistical data are presented as mean ± standard deviation (SD). All statistical calculations have been performed with SPSS v17.0 (Chicago, IL). The data were analyzed using unpaired t tests. A probability P < 0.05 was considered statistically significant.

Results

Changes of pulse frequency and energy tended to result in higher stone fragmentation efficiency in all of the cases at slower pulse rate but increased pulse energy (5 Hz/2.0 J) when compared against a higher pulse rate with decreased pulse energy (10 Hz/1.0 J). Thus, using a 365 μm fiber Ho:YAG laser disintegration was significantly more efficient with a mean increase of 27.5% applied to hard stones (all P < 0.05) and 33.6% when using soft stones (P < 0.05 in three of five groups) at 5 Hz/2.0 J (Table 1).

Table 1.

Effect of Pulse Energy and Frequency on Stone Disintegration (in mm ³): Comparison Between 10 Hz/1.0 J and 5 Hz/2.0 J Using a 365 μ m Fiber

	10 Hz/1.0 J	5 Hz/2.0 J	P value	Increase %
Hard stone mix
Sphinx (700 μsec)	46.07 ± 4.56	58.25 ± 3.80	<0.001	26.4
Sphinx (350 μsec)	49.00 ± 8.22	76.14 ± 5.11	<0.001	55.4
Odyssey 30 (700 μsec)	45.57 ± 4.40	50.14 ± 3.84	0.023	10.0
Odyssey 30 (350 μsec)	48.54 ± 4.95	62.07 ± 6.22	<0.001	27.9
Revolix Duo	54.71 ± 3.25	64.35 ± 3.84	<0.001	17.6
				27.5 mean
Soft stone mix
Sphinx (700 μsec)	51.67 ± 6.29	78.31 ± 5.63	<0.001	51.6
Sphinx (350 μsec)	81.14 ± 4.47	113.00 ± 4.28	<0.001	39.3
Odyssey 30 (700 μsec)	83.45 ± 16.81	95.95 ± 17.15	0.231	14.9
Odyssey 30 (350 μsec)	137.22 ± 27.44	211.67 ± 52.76	0.016	54.3
Revolix Duo	110.12 ± 10.86	118.98 ± 9.67	0.148	8.0
				33.6 mean

A very similar pattern was observed with the use of a 273 μm fiber in the same setting (Table 2). Switching from 10 Hz/1.0 J to 5 Hz/2.0 J consistently improved fragmentation efficiency on average 29.7% when applied to hard stones and 32.7% when applied to soft stones (all groups P < 0.05).

Table 2.

Effect of Pulse Energy and Frequency on Stone Disintegration (in mm ³): Comparison Between 10 Hz/1.0 J and 5 Hz/2.0 J Using a 273 μ m Fiber

	10 Hz/1.0 J	5 Hz/2.0 J	P value	Increase %
Hard stone mix
Sphinx (700 μsec)	43.00 ± 4.70	57.21 ± 4.55	<0.001	33.0
Sphinx (350 μsec)	48.50 ± 5.05	65.86 ± 6.29	<0.001	35.8
Odyssey 30 (700 μsec)	36.71 ± 3.35	50.93 ± 4.49	<0.001	38.7
Odyssey 30 (350 μsec)	42.57 ± 4.44	54.70 ± 4.13	<0.001	28.5
Revolix Duo	53.00 ± 4.48	59.64 ± 5.11	0.006	12.5
				29.7 mean
Soft stone mix
Sphinx (700 μsec)	52.57 ± 1.97	78.00 ± 7.67	<0.001	48.4
Sphinx (350 μsec)	82.93 ± 7.20	109.50 ± 5.49	<0.001	32.0
Odyssey 30 (700 μsec)	60.51 ± 3.95	76.31 ± 13.03	0.03	26.1
Odyssey 30 (350 μsec)	100.71 ± 20.50	138.10 ± 27.00	0.022	37.1
Revolix Duo	102.14 ± 6.26	122.39 ± 6.07	<0.001	19.8
				32.7 mean

Investigating the effect of variation in pulse length, a reduction of pulse length from 700 to 350 μsec tended to result in a higher stone disintegration in all tested groups both in hard and soft stones (Tables 3 and 4).

Table 3.

Effect of Pulse Length on Stone Disintegration (in mm ³): Comparison Between 700 μ sec and 350 μ sec Using a 365 μ m Fiber

	700 μsec pulse	350 μsec pulse	P value	Increase %
Hard stone mix
Sphinx (10 Hz/1.0 J)	46.07 ± 4.56	49.00 ± 8.22	0.33	6.4
Sphinx (5 Hz/2.0 J)	58.25 ± 3.8	76.14 ± 5.11	<0.001	30.7
Odyssey 30 (10 Hz/1.0 J)	45.57 ± 4.4	48.54 ± 4.95	0.174	6.5
Odyssey 30 (5 Hz/2.0 J)	50.14 ± 3.84	62.07 ± 6.22	0.001	23.8
				16.9 mean
Soft stone mix
Sphinx (10 Hz/1.0 J)	51.67 ± 6.29	81.14 ± 4.47	<0.001	57.0
Sphinx (5 Hz/2.0 J)	78.31 ± 5.63	113.00 ± 4.28	<0.001	44.3
Odyssey 30 (10 Hz/1.0 J)	83.45 ± 16.81	137.22 ± 27.43	0.001	64.4
Odyssey 30 (5 Hz/2.0 J)	95.95 ± 17.15	211.67 ± 52.76	0.002	120.6
				71.6 mean

With the use of a 365 μm fiber, this effect was most prominent in soft stone composition with a mean increase of fragmentation efficiency of 71.6% (all P < 0.05; Table 3). Applied to hard stones, the mean increase of fragmentation efficiency was 16.9%. In this group, a switch from 700 to 350 μsec displayed significantly higher disintegration rates in combination with a 5 Hz/2.0 J setting (+27.3%, all P < 0.05) but was insignificant with a 10 Hz/1.0 J setting (+6.5%, P > 0.05).

Again, reduction of pulse length in the 273 μm fiber group effected a higher stone disintegration in soft stones (+61.4%, all P < 0.05) and hard stones (+12.8%, three of four groups P < 0.05). This time, relative changes in stone fragmentation were independent of pulse rate and energy setting (Table 4).

Table 4.

Effect of Pulse Length on Stone Disintegration (in mm ³): Comparison Between 700 μ sec and 350 μ sec Using a 273 μ m Fiber

	700 μsec pulse	350 μsec pulse	P value	Increase %
Hard stone mix
Sphinx (10 Hz/1.0 J)	43.00 ± 4.70	48.50 ± 5.05	0.021	12.8
Sphinx (5 Hz/2.0 J)	57.21 ± 4.55	65.86 ± 6.29	0.002	15.1
Odyssey 30 (10 Hz/1.0 J)	36.71 ± 3.35	42.57 ± 4.44	0.004	16.0
Odyssey 30 (5 Hz/2.0 J)	50.93 ± 4.49	54.70 ± 4.13	0.067	7.4
				12.8 mean
Soft stone mix
Sphinx (10 Hz/1.0 J)	52.57 ± 1.97	82.93 ± 7.20	<0.001	57.8
Sphinx (5 Hz/2.0 J)	78.00 ± 7.67	109.50 ± 5.49	<0.001	40.4
Odyssey 30 (10 Hz/1.0 J)	60.51 ± 3.95	100.71 ± 20.50	0.004	66.4
Odyssey 30 (5 Hz/2.0 J)	76.31 ± 13.03	138.10 ± 27.00	<0.001	81.0
				61.4 mean

Using two different stone types, stone disintegration was in all of the tested settings significantly higher applied to soft stone compared with hard stone composition (all P < 0.05). Reduction of pulse length effected the most prominent changes of stone disintegration between soft and hard stones and achieved an increase of 120.5% at 350 μsec in stones compared with 49.9% at 700 μsec, whereas variation of pulse energy (+83.7% at 1.0 J/10 Hz and + 91.0% at 2.0 J/5 Hz) and fiber diameter (+80.21% 273 μm fiber and + 94.5% 365 μm fiber) showed comparable stone type related changes in mean increase.

A pairwise comparison between the 273 μm and the 365 μm fiber revealed a total increase of fragmentation efficiency of 12.3% (− 2.9 to +5 3.3%) when switching from the smaller to the larger fiber diameter and taking all experiments performed in this study together. We could not observe a general trend toward an increase of stone disintegration associated with differing fiber diameters: Using an OptiLite fiber, the fragmentation efficiency increased significantly in seven of eight comparisons (P < 0.05) at a higher fiber diameter. This trend, however, could not be confirmed when switching from a FlexiFib (273 μm) to a PercuFib (365 μm) fiber (10 of 12 compared groups P > 0.05).

Discussion

Minimally invasive stone surgery has undergone a development using evolving techniques in the past two decades. With the technical advance of semirigid and flexible ureteroscopic devices and the growing experience amongst urologists in endourologic techniques, high stone-free rates can be achieved while complication rates and perioperative morbidity could be lowered significantly.^11
–13 Stone disintegration can basically be achieved by ballistic, ultrasonic, electrohydraulic and laser devices.¹⁴

The Ho:YAG laser was shown to reliably disintegrate stones of all types and hardness, inclusive cystine stones.^10,13,15 Moreover, superior stone clearance rates, a better safety profile, and smaller size of yielding fragments in Ho:YAG laser lithotripsy compared with ballistic or electrohydraulic devices were reported.^4,16 Because of its versatility and flexibility, Ho:YAG laser lithotripsy with a 365 μm fiber is an excellent lithotrite for ureteral stones. Thinner laser fiber diameters are preferred in stone surgery for upper urinary tract stones because they do not limit angle deflection in flexible ureterorenoscopes, which is necessary for intracaliceal stone access.¹⁷

Because laser lithotripsy can be time consuming, techniques are needed for an efficient use of the holmium laser. Higher energy settings were shown to increase fragmentation efficiency.^6,8 Safety aspects and fiber characteristics, however, limit the use of high-power settings in ureteroscopy, especially when a thinner fiber is necessary in flexible ureteroscopy for intracaliceal stone management.^17
–19

We have chosen a standard power setting of 10W in the present study with the use of 273 μm and 365 μm fibers to have settings similar to a common ureteroscopic procedure. Even though some manufacturers limit the maximal output power when using smaller fibers to less than 10W because of the risk of fiber degradation, a standard power of 10W was maintained for all settings and fibers for better comparability between the devices in this study.

In the present study, the increase of pulse energy and the reduction of pulse length at a standardized power of 10W improved Ho:YAG laser fragmentation efficiency using non-floating phantom stones.

The holmium laser is a pulsed laser with a wavelength of 2,120 nm and a maximal absorption in water. Laser fragmentation can, in principle, be achieved by mainly two effects: Photoacoustic (mechanical) and photothermal.^20,21 The photoacoustic effect is characterized by the formation of a spherical plasma bubble formation. Bubble collapse leads to the generation of a shockwave, and the morphology of such shockwaves determines the effects on the target stone or tissue.²² A longer pulse length is related to the formation of an asymmetric bubble, resulting in a weak shockwave.²³ Hence, the photoacoustic effects were shown to have a more prominent effect in short-pulsed lasers and electrohydraulic devices but are negligible for the Ho:YAG laser fragmentation process.^23,24

Photothermal action, however, was demonstrated to be the leading mechanism of action on Ho:YAG laser lithotripsy.²⁴ First, direct absorption of the light energy induces a thermochemical reaction with a “meltdown” and vaporization of the stone and, second, vapor creation within the stone might contribute to stone cracking because of expansion.^20,21 Because of these characteristics, Ho:YAG laser lithotripsy produces smaller fragments than other lithotrites.¹⁶

Retropulsion of stone fragments is generated by photomechanistic and photothermal actions. Even if less retropulsion during Ho:YAG laser lithotripsy occurs compared with other lithotrites, it can complicate and extend a procedure or necessitate secondary procedures.^25,26 Factors that favor retropulsion during Ho:YAG laser lithotripsy were shown to be high output power, fiber diameter, and shorter pulse length.^7,9,26
–28 Several studies evaluated the effects of pulse width on retropulsion and stone fragmentation efficiency in vitro.^7,9,26,27 Consistent with other reports, two studies showed an increase in retropulsion but reduced stone fragmentation efficiency applying a higher pulse length setting of 700 μsec compared with 350 μsec.^7,9

Interestingly, after limitation of retropulsion using occlusion devices and a stone basket net fragmentation increased, but shorter pulse length was associated with similar or inferior fragmentation efficiency compared with higher pulse length, which is inconsistent with our results in the present work. We attribute this to differences in the model. In the two mentioned studies using smaller stones, retropulsion is limited but still possible within a range of a few millimeters, whereas our model uses larger stones within a rigid frame, where retropulsion is completely excluded.

The laser fiber and the energy delivered have significant impact on lithotripsy efficiency. Vassar and associates⁶ demonstrated that the energy density (J/cm²), defined by pulse energy output and laser diameter, determines Ho:YAG fragmentation efficiency. In our study, however, the switch from a 273 μm to 365 μm fiber diameter using the same power and pulse settings resulted in a higher disintegration rate of the Odyssey 30 but not of the Sphinx and the RevolixDuo laser. This indicates that an increase from a 273 μm to 365 μm fiber diameter is not necessarily associated with a higher stone disintegration in all cases but is, rather, dependent on the manufacturer and the laser and fiber characteristics. Differences between both manufacturers might be related to laser and fiber construction,¹⁹ even if we did not address this issue specifically in the present study. Furthermore, this implicates that our findings to increase Ho:YAG laser fragmentation efficiency by variation of pulse energy and pulse length in non-floating stones might be valid independently of manufacturer-specific fiber and laser characteristics.

We observed a tendency for larger fragments when using higher pulse energy in soft stones, which is, in our opinion, one of the reasons for a higher stone removal. We could not detect a relevant amount of fragments larger than 1 mm after sieving (data not shown), however.

Artificial stones, as used in the present series, differ in their composition from urinary stones in humans. Artificial stones, however, can be easily reproduced with a defined mass and density, and these invariable characteristics qualify them as an adequate model to study lithotripsy.^7,9,29 The two stone compositions used here, plaster of Paris (tensile strength 2.0 MPa) and T4 dental stone (∼ 3.1 MPa³⁰) do not specifically simulate a certain stone type but rather provide a model to cover the range from soft to hard human urinary stones (0.1–3.4 MPa). Teichman and colleagues¹⁰ demonstrated that Ho:YAG fragmentation efficiency varies with stone composition. Our study confirms this finding because stone disintegration increased from hard to soft stone composition. Our described mechanism to increase fragmentation efficiency by the use of higher pulse energy and shorter pulse length could be validated independently of stone composition in the present study.

Changes of pulse frequency, length, and energy can be performed easily and quickly in most laser devices. Our results may help to optimize Ho:YAG laser fragmentation efficiency in the clinical application. The urologist could adapt the laser settings specifically to the intraoperative stone situation, e.g. to increase pulse energy and reduce pulse length in case of impacted or very large urinary calculi or to decrease pulse energy and increase pulse length for small, floating stones for minimal retropulsion, using the same output power, respectively. Our results also indicate that in laser devices where adjustment of pulse length is unavailable, variation of the pulse frequency alone can optimize the fragmentation efficiency.

This study includes several limitations. An operator bias was present that we aimed to minimize by a single surgeon and an adequate number of sample size. As a result, low SD indicates a sufficient standardization and reproducibility of the procedure. As mentioned, artificial stones do not resemble urinary stones in every aspect. Therefore, the results obtained may not be transferable directly to the in vivo situation but rather provide relative values. Artificial stones, however, were previously shown to provide a reasonable model to investigate mechanisms of stone retropulsion and fragmentation.^7,9,29

Conclusion

We report that increase of pulse energy and reduction of pulse length at a standardized power of 10W improves Ho:YAG laser fragmentation efficiency in vitro in non-floating stones. These results were consistent using different fiber diameters, fiber types and stone compositions and were most prominent when applied to soft stones. Higher fiber diameter was not constantly associated with an increase in stone disintegration but rather manufacturer-dependent.

When applying these findings in clinical practice, an optimization of Ho:YAG laser lithotripsy can potentially be achieved in certain situations, such as impacted or large stones, where effects of retropulsion are excluded.

Footnotes

Disclosure Statement

No competing financial interests exist.

Abbreviations Used

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