3.5.1 Safeguard Conditions

Although the rooms of the clean operating department are classified by bacterial concentration, bacterial concentration cannot be effectively controlled or controlled throughout the whole process by hygienic disinfection alone; air cleanliness technology must serve as the necessary safeguard condition for achieving process control.

Emphasizing that air cleanliness is the necessary safeguard condition shows that a clean operating room is different from an ordinary operating room that has merely been disinfected; without air purification measures, it cannot be regarded as a clean room, thereby also pointing out the essence of the clean operating department.

More than 100 years ago, the British surgeon L. Sedea was the first to recognize the harmful effect of suspended contaminants on surgery. He used carbolic acid spray to disinfect the air during operations, and the mortality rate from postoperative infections was greatly reduced. For this he was generally acknowledged as the founder of aseptic surgery pioneers. However, carbolic acid made the air too unpleasant, and some surgical staff had to open the windows again for ventilation, which compromised the effectiveness of air disinfection. Nurse Nightingale (F. Nightingal) was the first person to emphasize the importance of clean, fresh air, and she also gave specific advice on how to achieve adequate ventilation. She believed that the most important task was to keep patients, as far as possible, constantly in clean outdoor air. Consequently, full fresh air remained for a long time the predominant form of operating room ventilation and air-conditioning systems. It was not until the 1930s that aseptic technique began to be widely accepted, and postoperative infections gradually dropped below 10%, which was already a remarkable advance at the time. In the following 30 years, people gradually became aware of the various contamination sources in operating rooms. Although the relative importance among these contamination sources has not been clarified to this day, it is generally believed that every route deserves attention.

In the late 1930s, ultraviolet radiation was adopted to reduce the hazard of suspended bacteria in the air, although it had been found early on that, apart from close-range irradiation, its bactericidal effect was very limited.

After World War II, people had already recognized the limitations and side effects of relying solely on chemicals for disinfection and sterilization; the massive use of antibiotics not only caused patients to develop drug-resistant strains but also suppressed the normal bacterial flora and lowered immune function. Only then did attention turn again to physical bacteria-removal methods, such as borrowing industrial clean technology. Operating room ventilation systems began to require high-efficiency air filters, and partial air recirculation (return air) was allowed in the ventilation and air-conditioning systems. Owing to the effectiveness and irreplaceability of clean technology, biological clean technology gradually matured in the British healthcare field and was rapidly popularized.

【Reference】

① The equivalent diameter of microorganisms.

Like dust, microorganisms are treated as particles in the field of air cleaning technology. As particles, their naked size should not be considered; rather, they should be viewed together with their carriers. Biological particles generally cannot float in the air alone; instead, they exist on larger non-living particles. Depending on different needs, three different equivalent diameters can be used to describe them, while for their settling phenomenon, the settling equivalent diameter can be used. The settling equivalent diameter is the particle diameter equivalent to that at which the bacterial population has the same settling amount, i.e., the same settling velocity $v_s$.

The settling equivalent diameter $d_p(mu m)$ of an arbitrary carrier particle with a density of $rho$ is given by the following formula:

$$d_p = left[frac{v_s}{0.6 times 10^{-2},dfrac{rho}{2}}right]^{frac{1}{2}}$$

$$v_s = frac{N_g}{NfT}(text{cm/s})$$

where: $N_g$——bacterial settling amount (count);

$N$——airborne bacterial concentration (count/cm³);

$T$——sampling time, i.e., settling time (s).

If the airborne bacterial concentration is measured and the settled bacterial concentration is measured as well, $d_p$ can be obtained from the above formula. According to relevant measured data, the settling equivalent diameter $d_p$ calculated by the above formula with $rho=1$ is between 6～9μm for ordinary operating rooms without air cleaning, averaging 7.36μm; for rooms with air cleaning, such as clean operating rooms, it is between 3～8μm, averaging 5.5μm. If $rho$ is taken as 1.5, the above averages are 6.01μm and 4.49μm, respectively. Therefore, the settling velocity of bacteria-carrying particles must never be imagined from the size of the naked bacterial particles—it seems extremely small, but in fact a 5μm particle takes only about 0.5h to settle from the ceiling to a tabletop. Although viruses are only 0.01～0.1μm, the above equivalent diameter principle also applies to them. When viruses at $10^{12}～10^{16}$ /mL were sprayed into the air in the experiment, it was found that the phages mainly landed on stages Ⅲ～Ⅳ of the Andersen sampler, i.e., their main size was 2～5μm.

Table 3.23 lists some experimental reports, from which it can be seen that the penetration of the filters for phages or viruses whose own size is below 0.1μm is far smaller than the rated penetration of the filters (for 0.3μm DOP). This shows that the filtration efficiency of high-efficiency filters for viruses is far greater than that for the efficiency for 0.3μm particles; therefore, the equivalent diameter of viruses should be much larger than 0.3μm, which is consistent with the aforementioned results of virus sampling with the Andersen sampler.

② The comparison of filter penetration rates is shown in Tables 3.23～3.25.

Table 3.23 Comparison of Filter Penetration Rates

Filter Air volume/(m³/h) Pressure drop/Pa Penetration (%) for bacteriophage T1 /×0.1μm Penetration (%) for viruses /×0.3μm Penetration (%) for foot-and-mouth disease virus /×(0.01～0.012)μm Penetration (%) for DOP /×0.3μm
HEPA filter A 42.5 264 0.0039 0.011
HEPA filter B 42.5 175 0.00085 0.02
HEPA filter C 42.5 125 0.00085 0.006
HEPA filter D — — 0.003 0.0036 0.001 0.01

Note: All major industrialized countries emphasize only air filters of different efficiencies as the safeguard means for clean operating rooms.

Table 3.24 Filter Grades Specified by the Two Safeguard Means for Clean Operating Rooms

Grade German standard [DIN1946/4(1989)] Swiss standard (SKI1987) British standard (1983,1986)
General EU4+EU7+S EU5+EU8+EU11 EU3+EU7
High grade EU4+EU7+S EU5+EU8+EU11 EU3+EU7+EU9

Note: For EU4 etc., see the explanation of Table 3.9; EU11 has a colorimetric efficiency ≥99.95%; the main difference between the general and high grades lies in the air volume.

Table 3.25 Final Filter Efficiency Specified by the Safeguard Means for Clean Operating Rooms in Japan (1998)

Class Name Final filter efficiency/%
Ⅰ Highly clean area DOP efficiency＞99.97
Ⅱ Clean area DOP efficiency＞95
Ⅲ Quasi-clean area DOP efficiency＞90
Ⅳ Generally clean area DOP efficiency＞60
Ⅴ Contamination control area DOP efficiency＞60

Note: In the 1989 edition of the standard, the efficiency values were lower than those in the 1998 edition, which shows the emphasis placed on air cleaning measures as safeguard conditions.

3.5.2 Removal Efficiency

Precisely because the bacteria and virus particles suspended in the air are relatively large, barrier-type air filters have a relatively high filtration removal efficiency against them.

In terms of bacterial removal efficiency, medium-efficiency filters can reach 70%～80%, medium-high-efficiency filters can reach 90%～99%, sub-high-efficiency filters can reach 99%～99.9%, and HEPA filters can approach 100%, which is unmatched by other disinfection methods.

[Reference]

① The comparison of sterilization effects is shown in Table 3.26. Table 3.26　Comparison of the bactericidal effects of different disinfection methods

Disinfection method Bacterial count before disinfection/(count/m³) Bacterial count after disinfection/(count/m³) Bactericidal rate/%
Atractylodes 642 204 68.22
Ozone disinfection machine 673 55 91.82
Ultraviolet radiation 601 103 82.86
Formaldehyde 598 135 77.42
Negative ion generator 1 734 461 73.4
Electronic sterilization lamp 1 711 257 85.0

② The evaluation of ultraviolet sterilization is shown in Table 3.27.

Table 3.27　Evaluation of ultraviolet sterilization in foreign GMP

GMP Clause Evaluation
WHO(1992) 17.34 Due to the limited effectiveness of ultraviolet radiation, ultraviolet sterilization cannot replace chemical disinfection
WHO(1992) 17.65 Ultraviolet irradiation must not be used for terminal sterilization
EEC(1992) Annex—Manufacture of Sterile Medicinal Products 70 In general, ultraviolet radiation cannot be used as a sterilization method
Eu(1996) Annex—Manufacture of Sterile Medicinal Products 70 In general, ultraviolet radiation is not an acceptable disinfection method

3.5.3　It Has Been Confirmed That Clean Operating Rooms Can Substantially Reduce Postoperative Infection

A typical report is that the British doctor Charnley applied unidirectional flow technology at Wrightington Hospital for more than 10 years, reducing the hospital's postoperative infection rate from 7%–9% to below 1%, and eventually to below 0.5%. As a result of promoting this technology throughout the UK, the average infection rate of hip joint replacement surgery dropped from 9.5% at that time to 1.1%.

In China, Shanghai Changzheng Hospital performed 9337 operations in clean operating rooms from 1989 to 1990 without a single infection, and Beijing 301 Hospital performed 16 427 operations from the end of 1994 to the end of 1996 without a single infection. Of course, other factors were also involved here.